The DOI matches its Crossref record; 129 of the 130 references it cites were found in a registry or an index; 55 of the 106 sources its claims cite were checked for support.
Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria
Open accessAbstract
Mycobacteria inhabit a wide range of intracellular and extracellular environments. Many of these environments are highly dynamic and therefore mycobacteria are faced with the constant challenge of redirecting their metabolic activity to be commensurate with either replicative growth or a non-replicative quiescence. A fundamental feature in this adaptation is the ability of mycobacteria to respire, regenerate reducing equivalents and generate ATP via oxidative phosphorylation. Mycobacteria harbor multiple primary dehydrogenases to fuel the electron transport chain and two terminal respiratory oxidases, an aa3 -type cytochrome c oxidase and cytochrome bd-type menaquinol oxidase, are present for dioxygen reduction coupled to the generation of a protonmotive force. Hypoxia leads to the downregulation of key respiratory complexes, but the molecular mechanisms regulating this expression are unknown. Despite being obligate aerobes, mycobacteria have the ability to metabolize in the absence of oxygen and a number of reductases are present to facilitate the turnover of reducing equivalents under these conditions (e.g. nitrate reductase, succinate dehydrogenase/fumarate reductase). Hydrogenases and ferredoxins are also present in the genomes of mycobacteria suggesting the ability of these bacteria to adapt to an anaerobic-type of metabolism in the absence of oxygen. ATP synthesis by the membrane-bound F1FO-ATP synthase is essential for growing and non-growing mycobacteria and the enzyme is able to function over a wide range of protonmotive force values (aerobic to hypoxic). The discovery of lead compounds that target respiration and oxidative phosphorylation in Mycobacterium tuberculosis highlights the importance of this area for the generation of new front line drugs to combat tuberculosis.
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Claims the paper makes
27 No full text of the sources · 24 Partly supported · 17 Supported · 17 No basis given · 9 Own interpretation · 4 Sources not found · 3 Supported so far · 3 Couldn’t confirm · 2 Not checked yet · 1 Not supported · 1 Own result · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“The bc1-aa3 pathway appears to be the major respiratory route in mycobacteria under standard aerobic culturing conditions (70).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Complex III and IV of the M. tuberculosis electron transport chain
What the sources say
- Supportedcites [70] source
The Discussion states that growth impairment in M. smegmatis mutants confirms the bc1-aa3 pathway is the major respiratory route in actinomycetes under standard aerobic culturing conditions. This supports the claim about mycobacteria; the supplied passage has no page number. (LLM, conf=0.94)
- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Four different types of hydrogenases are found in mycobacteria and are annotated to be of the NiFe type.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results section, ‘Hydrogenase Gene Clusters in M. smegmatis and Characterization of a Hydrogenase Mutant’ (page unavailable), reports three different putative hydrogenase complexes in M. smegmatis, not four. It predicts a Ni-Fe or Ni-Fe-Se center for all three, supporting the NiFe characterization but not the claimed count of four types in mycobacteria. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several studies have suggested that ndh is essential for growth of M. tuberculosis (12, 26, 28, 29) (Table 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Supportedcites [12] source
The Discussion reports that no viable M. tuberculosis strain with an insertionally inactivated ndh was obtained, suggesting a lethal phenotype. This supports the citing sentence’s hedged claim that ndh is essential for growth, although the paper frames its broader respiratory conclusion around aerobic growth. (LLM, conf=0.91)
- Could not verifycites [26] sourceExperimental — accuracy not yet measured
The Results section describes genome-wide predictions of genes required for M. tuberculosis growth, but the passages retrieved do not identify ndh as one of them. Searches for “ndh,” “Rv1854c,” and NADH dehydrogenase found no passage in our copy that addresses ndh essentiality; page numbers were unavailable. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [28] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a recent study it was shown by 13C flux analysis that M. tuberculosis grown under hypoxia metabolizes glucose through a reverse TCA cycle to generate succinate as an excreted fermentation end product (42).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Supportedcites [42] source
The Results section, “Stable isotope labeling studies support the reductive TCA cycle” (page not provided), reports that ¹³C-glucose labeling of hypoxic M. tuberculosis cultures produced labeled succinate in the supernatant, supporting flux through the reductive TCA branch. The Results also describe the shift to fermentative metabolism and succinate secretion under anaerobic conditions. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“M. smegmatis harbours three (designated Hyd1, 2 and 3) of the four hydrogenase complexes (16)”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results section, “Hydrogenase Gene Clusters in M. smegmatis and Characterization of a Hydrogenase Mutant” (page unavailable), identifies three putative hydrogenase gene clusters in the M. smegmatis genome. The cited paper does not establish the claimed total of four complexes or designate the three clusters Hyd1, Hyd2, and Hyd3. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“On the contrary, in a TraSH screen selecting for mutants that continue to replicate under hypoxic conditions Baek and coworkers (40) found SDH2 mutants overrepresented.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Partly supportedcites [40] sourceExperimental — accuracy not yet measured
The Identification of Growth-Regulatory Pathways and Transposon Site Hybridization sections describe a TraSH screen for mutants overrepresented after hypoxic culture. Our copy identifies tgs1 and dosR among the findings, but does not identify SDH2 mutants as overrepresented (also searched: SDH2, succinate dehydrogenase). The screen supports part of the claim; the specific SDH2 result is not supported by our copy. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“A recent transposon-site hybridization (TraSH) screen in M. tuberculosis suggested that SDH1 but not SDH2 was essential for growth under aerobic conditions on standard medium (26).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Could not verifycites [26] sourceExperimental — accuracy not yet measured
The Results section, “Comparison with previous studies” (page unavailable), discusses essentiality predictions and standard 7H10 medium, but does not identify SDH1 or SDH2. Searches for SDH1, SDH2, succinate dehydrogenase, and their gene identifiers found no passage in our copy establishing the claimed difference in essentiality. (LLM, conf=0.72)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“During carbon starvation and slow growth, mycobacteria switch to alternative electron donors (16, 20, 45) (Figure 2).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Supportedcites [16] source
The Abstract describes slow-growing M. smegmatis in carbon-limited culture using alternative electron donors under severe energy limitation. The Discussion section on adaptation to low growth rate likewise says mycobacteria switch to alternative primary dehydrogenases that supply reducing equivalents for respiration. No page numbers are available in our copy. (LLM, conf=0.90)
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
The Energy metabolism section (page not specified in our copy) reports downregulation of the primary aerobic respiratory chain during nutrient starvation and suggests that other enzymes may help recycle NAD+ or contribute to metabolism. It does not establish that mycobacteria switch to alternative electron donors during carbon starvation and slow growth; the tested condition was nutrient starvation in PBS. (LLM, conf=0.79)
- Not checked — no full text of the sourcecites [45] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hyd1, Hyd2 and Hyd3 are all soluble hydrogenases and found in mycobacteria of the slow-growing and fast-growing type, as well as pathogenic and non-pathogenic mycobacteria (16).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results section (page unavailable) identifies three putative hydrogenase complexes in M. smegmatis and predicts that all three are soluble. It does not establish that Hyd1, Hyd2 and Hyd3 occur across slow- and fast-growing, pathogenic and non-pathogenic mycobacteria; the Discussion instead describes a single putative membrane-bound hydrogenase cluster in M. tuberculosis. The claim also states solubility as established rather than predicted. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A knockout mutant of Hyd2 in M. smegmatis showed reduced biomass production when grown on complex medium under atmospheric conditions (16)”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Supportedcites [16] source
The Results section (page not specified) reports that the msmeg_2719 hydrogenase mutant produced 20% less biomass than the wild type during batch growth in LBT medium; Figure 5 identifies the complemented mutant as Hyd2. Materials and Methods (page not specified) describes the LBT batch cultures as shaken flasks, consistent with growth under atmospheric rather than oxygen-limited conditions. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
- It may state two separate claims as one. 63
- Probably not a substantial claim. 8
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“In M. tuberculosis, the bc1-aa3 pathway is essential for growth suggesting an inability of this bacterium to adapt in a manner analogous to M. smegmatis (70).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Complex III and IV of the M. tuberculosis electron transport chain
What the sources say
- Disputedcites [70] sourceExperimental — accuracy not yet measured
The Discussion describes the pathway’s essentiality in M. tuberculosis as apparent, based on failure to recover mutants under the conditions tested. Although it considers inability to adapt as a possibility, it concludes that respiratory adaptation probably does occur in M. tuberculosis; the mutants may instead grow too poorly to be detected. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Several studies have reported that nuo is down-regulated in M. tuberculosis during mouse lung infection (18), survival in macrophages (19), in both non-replicating persistence (NRP)-1 (1% oxygen saturation) and NRP-2 (0.06% oxygen saturation) relative to aerated mid-log growth (18), and upon starvation in vitro (20).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Supportedcites [18] source
The source reports decreased nuoB transcripts during mouse lung infection in Results and Discussion and a 3- and 6-fold decrease in NRP-1 and NRP-2, respectively, relative to aerated mid-log growth in “A Model of M. tuberculosis Respiratory Flexibility During Infection.” The macrophage-survival and starvation clauses have separate citations in the citing sentence and are not attributed to this source. (LLM, conf=0.94)
- Supportedcites [19] source
The “Energy Production During Anaerobic Respiration” section reports that genes encoding NADH dehydrogenase 1 (nuoABDFIL) were repressed in intraphagosomal M. tuberculosis relative to logarithmically growing bacteria. This supports the macrophage portion of the citing sentence, which is the portion attributed to this paper; the other conditions have separate citations. No page number is available in our copy. (LLM, conf=0.94)
- Supportedcites [20] source
The citation to this paper is attached to the in vitro starvation portion of the sentence, not the mouse, macrophage, or NRP conditions. The Energy metabolism section (pp. 717–731) reports that the nuoA–M operon is downregulated in the nutrient-starvation model. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Proline dehydrogenase is upregulated under both energy-limiting conditions and hypoxia (7, 16)”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results (Energy Metabolism; page unavailable) identify proline dehydrogenase as upregulated during energy-limited slow growth. The same section says that nearly all dehydrogenases upregulated during slow growth had very low mRNA levels under hypoxia, with hydrogenases the only exceptions. It therefore does not support the claim that proline dehydrogenase was also upregulated under hypoxia. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Gene expression studies suggest that Hyd1 and Hyd2 are used during nutrient starvation as an alternative electron source (Figure 2) while Hyd3 and the membrane-bound hydrogenase are more likely to have a function in disposing electrons under anaerobic conditions (16) (Figure 3).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results (Energy Metabolism; page unavailable) show that Hyd3 is upregulated under low oxygen, and the Discussion (Adaptation to Hypoxia; page unavailable) proposes hydrogen production as a redox sink under hypoxia. But the paper predicts all three hydrogenases to be soluble, not membrane-bound, and does not establish electron disposal as Hyd3’s specific function. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Hyd2 appears to be a founding member of the Group 5 high-affinity hydrogenases (52, 53).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Could not verifycites [52] sourceExperimental — accuracy not yet measured
The Discussion (p. 6) defines group 5 as a distinct group of putative high-affinity [NiFe]-hydrogenases. Searches for “Hyd2,” “hydrogenase 2,” and a founding member found no passage identifying Hyd2 or placing it in that group, so our copy does not establish the claim about Hyd2. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [53] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Hyd1 aligns closely with Group 2a uptake hydrogenases of the cyanobacteria such as Nostoc, indicating it oxidises H2 (51).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [51] sourceExperimental — accuracy not yet measured
The Introduction (page not available) places cyanobacterial uptake hydrogenases in group 2, and the H₂-production section says these enzymes oxidize H₂. The paper does not identify Hyd1 or report its alignment with cyanobacterial hydrogenases, so it does not establish that Hyd1 itself oxidizes H₂. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A more recent study suggests that the glyoxylate shunt, and not the reverse TCA, is used to metabolize both glycolytic and fatty acid carbon sources in response to oxygen limitation and this route also produces succinate as its metabolic end product (43).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Supportedcites [43] source
The Discussion states that the study identified the glyoxylate shunt as a pathway capable of metabolizing both glycolytic and fatty-acid carbon sources under oxygen limitation, producing succinate as an end product. The section on succinate-mediated maintenance of membrane potential explicitly contrasts ICL-mediated succinate production with production through the reverse TCA cycle. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“NDH-2 has not been reported in mammalian mitochondria leading to the proposal that these enzymes may represent a potential drug target for the treatment of human pathogens (6, 12, 27, 30, 31) and intracellular parasites (32).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Not checked — no full text of the sourcecites [6] source
- Supportedcites [12] source
The Discussion (page unavailable) states that human mitochondria use only type I NADH dehydrogenase and calls type II NADH dehydrogenase an important antimicrobial target. This supports the claim that NDH-2 is absent from mammalian mitochondria and has been proposed as a drug target. (LLM, conf=0.93)
- Supportedcites [27] source
The introductory passage (page unavailable) says NDH-2 is not found in mitochondria and describes it as essential to M. tuberculosis. The same section reports that phenothiazines inhibit NDH-2 and hinder M. tuberculosis growth, supporting the proposal that it may be a drug target. The paper does not establish that absence for every kind of mitochondrion; the citing claim is limited to mammalian mitochondria. (LLM, conf=0.87)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The second class is NDH-2, a non-proton translocating type II NADH dehydrogenase that does not conserve energy and is present in two copies (Ndh and NdhA) in M. tuberculosis (12) (Table 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Supportedcites [12] source
The Results section describes M. tuberculosis NDH-2 as a nonproton-pumping oxidoreductase present in two copies, ndh and ndhA. In this enzyme-level context, nonproton-pumping supports the characterization that NDH-2 does not conserve energy through proton translocation. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The authors propose that during oxygen limitation large amounts of succinate are produced by this pathway that are used to sustain the membrane potential, ATP synthesis and TCA cycle precursors akin to a “metabolic battery” (43).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Supportedcites [43] source
The Discussion states that, as oxygen is depleted, M. tuberculosis increases glyoxylate-shunt activity, produces large amounts of succinate, and can use it to sustain membrane potential, ATP synthesis, and anaplerosis depending on conditions. It also describes succinate as a multifunctional “metabolic battery” that sustains TCA cycle precursors. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It has been shown that M. smegmatis can grow on proline as the sole carbon and energy source and also that PRODH is an important electron donor, under both energy-limiting conditions and hypoxia (7, 16).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results > Energy Metabolism section (page unavailable) reports that proline dehydrogenase was among the proposed electron donors upregulated during slow growth under energy limitation. It does not establish that M. smegmatis grows on proline as its sole carbon and energy source or that PRODH is an important electron donor under hypoxia; the same section says nearly all dehydrogenases upregulated during slow growth had very low mRNA levels under hypoxia, except hydrogenases. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In fact, SDH1 and SDH2 have been shown to be differentially expressed under energy- or oxygen-limiting conditions in M. smegmatis (16). Under energy-limiting conditions SDH1 was upregulated 4-fold while SDH2 was downregulated 3-fold. Under oxygen-limiting conditions, SDH1 was downregulated 30-fold while SDH2 was upregulated 2-fold.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Weinstein et al. identified genes for two classes of NADH:menaquinone oxidoreductases in the genome of M. tuberculosis (12) (Table 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Supportedcites [12] source
The Results section states that the authors identified two types of NADH dehydrogenase in the M. tuberculosis genome: the 14-subunit NDH-1 encoded by nuoABCDEFGHIJKLMN and NDH-2 present in two copies, ndh and ndhA. This directly supports the attributed identification. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It has been shown that M. smegmatis, among other mycobacterial species, can oxidize molecular hydrogen in the presence of carbon monoxide (CO), implying that M. smegmatis expresses a functional hydrogenase (54).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [54] sourceExperimental — accuracy not yet measured
The Results report H₂ uptake by M. smegmatis, supporting the inference that it has a functional hydrogen-oxidizing enzyme. They report CO uptake separately, however, and do not establish that H₂ oxidation occurred in the presence of CO; the paper does not directly identify a hydrogenase. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The membrane-associated malate quinone oxidoreductase (MQO) oxidizes malate to oxaloacetate and transfers the reducing equivalents to menaquinone (MK) (59, 60) (Figure 3).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [59] source
- Partly supportedcites [60] sourceExperimental — accuracy not yet measured
The introductory passage and the L-malate oxidation section state that Mqo oxidizes malate to oxaloacetate and donates electrons at the quinone pool; the latter section demonstrates reduction of ubiquinone-1. The paper does not establish menaquinone specifically as the electron acceptor: it says the natural direct acceptor is most likely a quinone, while menaquinone-4 did not stimulate activity in the reported assay. No page number is available in our copy. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TMC207 is bactericidal towards most species of mycobacteria (109), but is only bacteriostatic against M. avium (118) and M. smegmatis (Berney and Cook, unpublished data).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > ATP Synthesis by the F1Fo ATP Synthase
What the sources say
- Partly supportedcites [109] sourceExperimental — accuracy not yet measured
The Chemistry and in vitro anti-mycobacterial activity section reports bactericidal activity against M. tuberculosis and low MICs for several other mycobacterial species. Low MICs do not establish that the drug is bactericidal against most species. The M. avium and M. smegmatis clauses cite different sources, so they are not judged against this paper; page numbers are unavailable in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [118] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, a subsequent study has reported that the nirA gene is misannotated and is in fact sirA, a sulfite reductase shown to be essential for growth on sulfate or sulfite as the sole sulfur source (93) (Table 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
What the sources say
- Supportedcites [93] source
The Abstract identifies sirA as a sulfite reductase originally misannotated nirA and states that its deletion prevents growth on sulfate or sulfite as the sole sulfur source. The Results specify that this growth finding comes from a Mycobacterium smegmatis deletion mutant. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F1Fo-ATP synthase and inhibit ATP synthesis (109, 111, 112).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > ATP Synthesis by the F1Fo ATP Synthase
What the sources say
- Partly supportedcites [109] sourceExperimental — accuracy not yet measured
The Chemistry and in vitro anti-mycobacterial activity section identifies the F0 subunit of ATP synthase as the target of the diarylquinoline R207910 and says the drug inhibits its proton pump. The Discussion says ATP synthase inhibition may lead to ATP depletion, but does not establish direct inhibition of ATP synthesis; nor does the paper rank diarylquinolines as the most promising compounds clinically. Page numbers are unavailable in our copy. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [111] source
- Supportedcites [112] source
The introduction (p. 2) identifies the diarylquinoline lead compound R207910 as being in Phase IIb clinical trials and says it specifically targets the c-subunit of F1F0-ATP synthase. The study summary (p. 2) reports that R207910 blocks ATP synthase activity, while the p. 3 passage describes inhibition of ATP synthesis and ATP depletion. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In M. tuberculosis, cytochrome bd is upregulated in the early stages of NRP-1 (i.e. decreasing oxygen) (68), in NRP-2 (18) and in response to nitric oxide (NO) (18).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Terminal Electron Acceptor Utilization
What the sources say
- Not checked — no full text of the sourcecites [68] source
- Supportedcites [18] source
The citation to this paper is attached to NRP-2 and nitric oxide, not early NRP-1, which has a separate citation. In “A Model of M. tuberculosis Respiratory Flexibility During Infection,” the paper reports that bd-type oxidase genes were upregulated under both NRP-2 and NO treatment; the provided passages do not give page numbers. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sohaskey (91) has reported that exogenously supplied nitrate has no effect on long-term persistence during gradual oxygen depletion, but played an important role during rapid adaptation to hypoxia (< 18 h).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
What the sources say
- Partly supportedcites [91] sourceExperimental — accuracy not yet measured
The Results report that nitrate had no effect on survival during gradual oxygen depletion and improved survival after sudden anaerobiosis. However, the <18 h threshold describes how quickly anaerobic conditions were created, not how long hypoxia lasted; survival was tracked for 26 days. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast, fumarate reductase, nitrate reductase and NDH-2 are all upregulated under these conditions (19).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Terminal Electron Acceptor Utilization
What the sources say
- Supportedcites [19] source
The Energy Production During Anaerobic Respiration section states that frdA, narX, and ndh—encoding fumarate reductase, nitrate reductase, and NDH-2—were induced in intraphagosomal M. tuberculosis. The paper specifies that narX induction occurred only in activated macrophages. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In M. tuberculosis, the atp operon is downregulated during growth in macrophages (19), the mouse lung and in cells exposed to NO or hypoxia (18).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > ATP Synthesis by the F1Fo ATP Synthase
What the sources say
- Supportedcites [19] source
The Expression Profiling of Intraphagosomal MTB section identifies the ATP-synthase genes in cluster III as a putative operon of repressed genes. This supports the macrophage-growth portion attributed to this paper; the mouse-lung, NO, and hypoxia portion is attached to a different citation. (LLM, conf=0.91)
- Partly supportedcites [18] sourceExperimental — accuracy not yet measured
The Results and Discussion report decreased atpA and atpD expression during chronic mouse-lung infection. The section on in vitro respiratory flexibility reports that both transcripts decreased under oxygen depletion, but its discussion of NO-treated cells does not establish downregulation of the atp genes. The macrophage portion is cited to a different source (19), not this paper (18). (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These data suggest that Hyd2 oxidizes hydrogen at very low concentrations, which fits with its purported role as a high-affinity hydrogenase (52).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Partly supportedcites [52] sourceExperimental — accuracy not yet measured
The Results (p. 3) identify a putative high-affinity [NiFe]-hydrogenase in S. avermitilis, and the Discussion (p. 6) describes high-affinity H₂ oxidation in Streptomyces isolates possessing the relevant genes. These passages support the proposed role of that hydrogenase group, but the paper does not identify Hyd2 or establish that Hyd2 itself oxidizes H₂ at very low concentrations. (LLM, conf=0.78)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, in E. coli, cytochrome bo (Km for oxygen in the micromolar range) and cytochrome bd (Km for oxygen in the nanomolar range) (63, 64) are coordinately regulated by the ArcBA system and transcriptional regulator FNR (65).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Terminal Electron Acceptor Utilization
What the sources say
- Not checked — no full text of the sourcecites [63] source
- Not checked — no full text of the sourcecites [64] source
- Partly supportedcites [65] sourceExperimental — accuracy not yet measured
The Abstract and Introduction (page not available) state that ArcA/ArcB and Fnr regulate the cytochrome bd (cydAB) operon. The paper contrasts cytochrome bo and bd expression as oxygen becomes limiting, but its substantive passages do not establish that both oxidases are coordinately regulated by both regulators. The oxygen-Km values are attached to other citations in the citing sentence, not to this paper. (LLM, conf=0.79)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“M. smegmatis lacks an MDH homologue and it was shown that MQO responded to low oxygen concentration with 4-fold increase in gene expression (16).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Supportedcites [16] source
The Results section (“TCA and Glyoxylate Shunt Pathways”; page not provided) states that M. smegmatis lacks NAD+-dependent malate dehydrogenase and that MQO was upregulated fourfold under hypoxia, compared with growth at 50% oxygen saturation. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When slow growing cells of M. smegmatis (70 h doubling time), with low levels of atp operon expression, are exposed to hypoxia (0.6% oxygen saturation), the atp operon is upregulated 3-fold suggesting an important role for this enzyme during adaptation to hypoxia (16).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > ATP Synthesis by the F1Fo ATP Synthase
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Results (Energy Metabolism; page not available) report that the F1Fo-ATP synthase gene cluster was downregulated during slow growth at 50% oxygen saturation, supporting the claim of low expression. The paper also studies slow-growing cells at 0.6% oxygen saturation, but its account of the hypoxic response does not report threefold upregulation of the atp operon or assign that operon an important role in hypoxia adaptation; it instead highlights oxidases and hydrogenases. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Induction of EHR was independent of DosR, suggesting that other sensory and regulatory mechanisms must exist to signal prolonged exposure to hypoxia.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Control of electron transport chain expression and oxidative phosphorylation
What the sources say
- Supportedcites [125] sourceExperimental — accuracy not yet measured
The Results section ('The EHR and the DosR regulon'; page unavailable) reports that nearly all later-induced genes were also induced in the dosR mutant. The Discussion (page unavailable) likewise says disrupting the DosR regulon had very little effect on EHR expression and describes regulatory factors within the EHR. The proposed involvement of other mechanisms is consistent with those findings, though the paper does not identify a specific sensor for prolonged hypoxia. (LLM, conf=0.88)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast, a set of 230 genes was significantly up-regulated at four and seven days of hypoxia, but not initially, and were termed the enduring hypoxic response (EHR) (125).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Control of electron transport chain expression and oxidative phosphorylation
What the sources say
- Supportedcites [125] source
The Results section, “The Enduring Hypoxic Response (EHR),” defines the EHR as MTB genes not induced initially but significantly upregulated at four and seven days of hypoxia. It states that 230 genes meet those criteria. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“However, the fourth putative hydrogenase is only found in pathogenic mycobacteria (including M. tuberculosis complex) and seems to be restricted to slow-growers (Table 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not matchedcites Table 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Interestingly, a proC mutant of M. tuberculosis was avirulent in immunocompetent mice, however this was not due to its inability to proliferate intracellulary because bacterial loads increased in the mouse lungs after 20 days post infection (49).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [49] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The addition of TMC207, a specific inhibitor of the F1FO-ATP synthase, was bactericidal against hypoxic, non-replicating M. tuberculosis, but had no effect on the ΔΨ (6).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
- Not checked — no full text of the sourcecites [6] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early studies on respiration demonstrated that Mycobacterium tuberculosis H37Rv, grown in the lungs of infected mice, had high rates of endogenous respiration that were not stimulated by exogenous substrates (e.g. acetate, pyruvate, glucose, glycerol, lactate) (1). In contrast, cells grown in vitro respired these substrates at high rates.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Overview of mycobacterial respiration and oxidative phosphorylation
What the sources say
- Not checked — no full text of the sourcecites [1] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Mutations in the ndh gene of M. smegmatis result in a pleitropic effect: temperature sensitivity, amino acid auxotrophy and resistance to the first-line anti-TB drug isoniazid (INH) and its analog and second-line anti-TB drug ethionamide (ETH) (14, 15).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Measured experimental values for mycobacteria oxidizing NADH or succinate yield P/O ratios of 0.52, and 0.36, respectively (5).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
- Not checked — no full text of the sourcecites [5]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Rao et al. (6) have reported that hypoxic, non-replicating M. tuberculosis generate a total PMF of −113 mV, −73 mV of electrical potential (ΔΨ) and −41 mV of ZΔpH.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
- Not checked — no full text of the sourcecites [6] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“only two terminal respiratory oxidases present in mycobacteria, an aa3-type cytochrome c oxidase (encoded by ctaBCDE) belonging to the heme-copper respiratory oxidase family and cytochrome bd-type menaquinol oxidase (cydABCD) (Figure 1).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Overview of mycobacterial respiration and oxidative phosphorylation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Growth of mycobacteria is sensitive to compounds that dissipate the membrane potential (e.g. protonophores and valinomycin) and these compounds are bactericidal towards growing and non-growing (aerobic or hypoxic) cells”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The addition of thioridazine, a compound that targets NDH−2, results in dissipation of the ΔΨ and significant cell death suggesting that NADH is an important electron donor for the generation of the ΔΨ under hypoxic conditions.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
- Not checked — no full text of the sourcecites [6] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Proline can be utilized as an electron donor as well as a carbon and nitrogen source (Figure 2).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The PMF-generating machinery in mycobacteria comprises three energy-conserving steps: complex I (4H+/2e−), complex III (menaquinol-cytochrome c oxidoreductase, 4H+/2e−) and complex IV (2H+/2e−) suggesting that the overall proton translocation stoichiometry for the transfer of 2e− from NADH to oxygen is 10H+/2e−.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Irrespective of the oxygen concentration or the protonmotive force (PMF), ATP synthesis is obligatorily coupled to the electron transport chain and the F1Fo-ATP synthase”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Overview of mycobacterial respiration and oxidative phosphorylation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Fatty acids, however, stimulated the respiration of in vivo grown M. tuberculosis, suggesting for the first time that M. tuberculosis switches to different energy sources in host tissues to fuel respiration.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Overview of mycobacterial respiration and oxidative phosphorylation
What the sources say
- Not checked — no full text of the sourcecites [1] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that SDH1 could be the dedicated succinate dehydrogenase and SDH2 catalyses fumarate reductase activity, which is important for survival under hypoxia.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“NDH-1 is encoded by the nuoABCDEFGHIJKLMN operon and transfers electrons to menaquinone, conserving energy by translocating protons across the membrane to generate a PMF (Figure 2).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As an exception among mycobacteria, M. tuberculosis encodes a third complex (frdABCD) that is annotated as a fumarate reductase (Table 1) and is absent in all other pathogenic strains like Mycobacterium avium paratuberculosis, Mycobacterium marinum, Mycobacterium ulcerans and M. leprae.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Succinate dehydrogenase forms complex II of the respiratory chain and couples oxidative phosphorylation to central carbon metabolism by being an integral part of the TCA cycle (Figure 2).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In bacteria three different types of respiratory NADH dehydrogenases have been identified and characterized on the basis of reaction mechanism, subunit composition and protein architecture (11). These include the proton-pumping type I NADH dehydrogenase (NDH-1, complex I), non-proton pumping type II NADH dehydrogenase (NDH-2) and sodium-pumping NADH dehydrogenase (NQR).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Proton-pumping type I NADH dehydrogenase and non-proton pumping type II NADH dehydrogenase
What the sources say
- Not checked — no full text of the sourcecites [11] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mycobacteria generally grow at neutral pH and under these conditions generate a PMF of approximately −180 mV (4).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Energetics of mycobacteria during growth and non-growth conditions
What the sources say
- Not checked — no full text of the sourcecites [4] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the absence of oxygen, mycobacterial growth is inhibited, even if alternative electron acceptors are present (e.g. nitrate, fumarate).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Overview of mycobacterial respiration and oxidative phosphorylation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“In fact, it has been proposed that fumarate may be an important endogenous electron acceptor for energy production and maintenance of redox balance (oxidation of NADH to NAD+) in hypoxic non-replicating mycobacteria (6).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
What the sources say
- Not checked — no full text of the sourcecites [6] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Hydrogenases catalyze the reversible oxidation of molecular hydrogen: 2H+ + 2e−→ H2 and play a central role in energy metabolism of bacteria, archaea and eukarya (50).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not matchedcites [50]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that SDH2 has a pivotal role in the transition of M. tuberculosis from aerobic to hypoxic conditions and supports the hypothesis of it being a fumarate reductase.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Multiple succinate dehydrogenases and fumarate reductase: an essential link between central metabolism and respiration in mycobacteria
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The cytochrome bd branch is bioenergetically less efficient (non-proton translocating) and is synthesized at low oxygen tensions in mycobacteria (67).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Cytochrome bd-type oxidase
What the sources say
- Not checked — no full text of the sourcecites [67] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Ehr enzymes lack the cysteine residues needed to ligate a [NiFe] center, which is the catalytic center of hydrogenases. Additionally, no maturation factors to synthesize these complex centers are present in M. tuberculosis.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It has been shown that M. tuberculosis H37Ra, which possesses CO-DH activity, can grow on CO as a sole source of carbon and fuel for energy generation (56) (Figure 2).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [56] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The M. tuberculosis narK2 was shown to complement this E. coli double mutant, supporting a role for narK2 in nitrate reduction by coding for a transporter of nitrate into and nitrite out of the cell (85).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
What the sources say
- Not checked — no full text of the sourcecites [85] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This strategy does not appear to be exploited by M. smegmatis: the F1Fo-ATP synthase is essential for growth even on fermentable substrates, suggesting that ATP production from substrate level phosphorylation alone, despite increased glycolytic flux, may be insufficient to sustain growth of these bacteria (103).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > ATP Synthesis by the F1Fo ATP Synthase
What the sources say
- Not checked — no full text of the sourcecites [103] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data support the proposal that nitrite produced by nitrate reductase is not converted to ammonium, but instead is exported from the cell by NarK2.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: M. tuberculosis cannot reduce nitrite.
In the paper
“Carbon monoxide dehydrogenase (CO-DH) is responsible for the oxidation of CO to carbon dioxide (CO2) in carboxydobacteria, which grow on CO as a sole source of carbon and energy (55).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not checked — no full text of the sourcecites [55] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sohaskey and Wayne demonstrate that overexpression of recombinant M. tuberculosis nitrate reductase in either M. tuberculosis or M. smegmatis (low nitrate reductase activity) does not confer the ability of these cells to grow anaerobically i.e. no growth of either species is observed with nitrate anaerobically even though the nitrate reductase activity of whole cells increases (85).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
What the sources say
- Not checked — no full text of the sourcecites [85] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The evolution of H2 is a mechanism commonly employed by anaerobic bacteria to recycle reducing equivalents obtained from anaerobic degradation of organic substrates.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The M. smegmatis cydA mutant showed a reduced growth rate at 0.5–1 % air saturation and also a 10-fold difference in CFU after 140 h of growth in the presence of cyanide at 21% air saturation when co-cultured with wild-type M. smegmatis (67).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Cytochrome bd-type oxidase
What the sources say
- Not checked — no full text of the sourcecites [67] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No function has yet been proposed for Ehr enzymes, but its homology to hydrogenases and to proton-pumping type I NADH dehydrogenases points to a role in energy metabolism.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“M. tuberculosis harbors a copy of MQO and a cytoplasmic NAD+-dependent malate dehydrogenase (MDH) (61, 62).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
What the sources say
- Not matchedcites [61]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [62] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these observations, it is apparent that this enzyme does not support anaerobic growth of mycobacteria and therefore the role of this enzyme in the physiology of mycobacteria is unclear.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Singh and colleagues report that WhiB3 contains a 4Fe-4S cluster, which binds NO (121).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Control of electron transport chain expression and oxidative phosphorylation
What the sources say
- Not checked — no full text of the sourcecites [121] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It is proposed that NarK2 senses the redox state of the cell, possibly by monitoring the flow of electrons to cytochrome oxidase, and adjusts its activity so that nitrate is transported under reducing, but not under oxidizing conditions (86).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
What the sources say
- Not checked — no full text of the sourcecites [86] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the absence of oxygen, alternative electron acceptors (e.g. nitrate and fumarate) are available for mycobacterial metabolism, but none of these electron acceptors have been shown to support growth of mycobacterial species.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“During aerobic respiration, energy is conserved by the generation of a PMF across a proton-impermeable membrane.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Terminal Electron Acceptor Utilization
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A striking observation is that neither Dos nor WhiB3 controls any component of the electron transport machinery in M. tuberculosis.”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Control of electron transport chain expression and oxidative phosphorylation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The authors state this as an assumption.
The aa3-type cytochrome c oxidase and cytochrome bd-type oxidase of mycobacteria have markedly different affinities for oxygen.
“The rationale for this coordinated expression is largely based on the assumption that the mycobacterial aa3-type cytochrome c oxidase and cytochrome bd-type have markedly different affinities for oxygen in mycobacteria, but this remains to be experimentally shown.”
The paper relies on this without support.
Mycobacteria are obligate aerobes.
“Mycobacteria are obligate aerobes and as such have to possess mechanisms to detect the ambient oxygen tension”
The paper relies on this without support.
M. tuberculosis cannot reduce nitrite.
“Since M. tuberculosis is unable to reduce nitrite, which could accumulate to toxic levels, it must be exported out of the cell.”
The paper relies on this without support.
Mycobacterial genomes lack genes for soluble or membrane-bound cytochrome c.
“Mycobacterial genomes do not appear to harbor genes for either a soluble or membrane-bound cytochrome c”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Electron acceptor utilization under hypoxia
“One belongs to Group 2 cytoplasmic bidirectional hydrogenases and can be found in some slow-growing (e.g. M. marinum and M. kansasii) and fast-growing (e.g. M. smegmatis) mycobacteria. In M. smegmatis, this enzyme is termed Hyd3 and has been shown to respond strictly to oxygen-limiting conditions with up to 50-fold increase in gene expression (16).”
§ Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria > Alternative electron donor utilization during starvation and hypoxia
“In contrast, Hyd3 is closely related to the Group 3 cytoplasmic bidirectional hydrogenases.”
Citations
Cites
Genes required for mycobacterial growth defined by high density mutagenesis
Sassetti, C. M., Boyd, D. H., & Rubin, E. J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03425.x · Cited by 2,544 · cited 1×
“smegmatis has been shown to be essential for optimal growth (29, 103).”
BackgroundA Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis
Andries, K., Verhasselt, P., Guillemont, J., Göhlmann, H. W. H., Neefs, J.-M., Winkler, H., Van Gestel, J., Timmerman, P., Zhu, M., Lee, E., et al. (2005) · Science · doi:10.1126/science.1106753 · Cited by 2,191 · cited 5×
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F 1 F 0 -ATP synthase and inhibit ATP synthesis (109, 111, 112).”
BackgroundInfluentialMassive gene decay in the leprosy bacillus.
Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., Honoré, N., Garnier, T., Churcher, C., Harris, D., et al. (2001) · Nature · doi:10.1038/35059006 · Cited by 1,777 · cited 1×
“In contrast, the nuo operon has been lost from the genome of the intracellular parasiteMycobacterium leprae except for a single remaining nuoN pseudogene (13).”
BackgroundTranscriptional Adaptation of Mycobacterium tuberculosis within Macrophages
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030846 · Cited by 1,420
Betts, J. C., Lukey, P. T., Robb, L. C., McAdam, R. A., & Duncan, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02779.x · Cited by 1,395 · cited 3×
“…that nuo is down-regulated in M. tuberculosis during mouse lung infection ( 18), during survival in macrophages (19), in both nonreplicating persistence (NRP)-1 (1% oxygen saturation) and NRP-2 (0.06% oxygen saturation) relative to aerated mid-log growth (18), and upon starvation in vitro (20).”
BackgroundInfluentialGriffin, J. E., Gawronski, J. D., DeJesus, M. A., Ioerger, T. R., Akerley, B. J., & Sassetti, C. M. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002251 · Cited by 1,048 · cited 3×
“In some organisms with multiple type II NADH dehydrogenases, one copy appears more essential than the other, pointing to non-redundant functional differences (25, 26).”
BackgroundInfluentialInhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program
Voskuil, M. I., Schnappinger, D., Visconti, K. C., Harrell, M. I., Dolganov, G., Sherman, D. R., & Schoolnik, G. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030205 · Cited by 975 · cited 3×
“In addition to hypoxia, the Dos-regulon has also been shown to be activated by exposure of M. tuberculosis to NO or CO (88, 90, 120).”
BackgroundEnergetics of bacterial growth: balance of anabolic and catabolic reactions
Russell, J. B., & Cook, G. M. (1995) · Microbiological Reviews · doi:10.1128/mr.59.1.48-62.1995 · Cited by 927
Self-citationNonreplicating Persistence of Mycobacterium Tuberculosis
Wayne, L. G., & Sohaskey, C. D. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.139 · Cited by 807
Unden, G., & Bongaerts, J. (1997) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(97)00034-0 · Cited by 744 · cited 1×
“, fumarate) and noncoupling dehydrogenases such as NDH-2 are synthesized aerobically (21).”
BackgroundRegulation of the Mycobacterium tuberculosis hypoxic response gene encoding α-crystallin
Sherman, D. R., Voskuil, M. I., Schnappinger, D., Liao, R., Harrell, M. I., & Schoolnik, G. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121172498 · Cited by 735
Park, H., Guinn, K. M., Harrell, M. I., Liao, R., Voskuil, M. I., Tompa, M., Schoolnik, G. K., & Sherman, D. R. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03474.x · Cited by 712
Diarylquinolines target subunit c of mycobacterial ATP synthase
Koul, A., Dendouga, N., Vergauwen, K., Molenberghs, B., Vranckx, L., Willebrords, R., Ristic, Z., Lill, H., Dorange, I., Guillemont, J., et al. (2007) · Nature Chemical Biology · doi:10.1038/nchembio884 · Cited by 547 · cited 12×
“Research into mycobacterial respiration and oxidative phosphorylation has been energized by the discovery of a new drug (TMC207; Sirturo; Bedaquiline) that targets the ATP synthase of mycobacteria, suggesting that inhibitors of respiration and ATP synthesis will provide the next generation of front-line drugs to comba…”
BackgroundInfluentialRao, S. P. S., Alonso, S., Rand, L., Dick, T., & Pethe, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711697105 · Cited by 517 · cited 8×
“tuberculosis, the nuo operon is essential for neither growth nor persistence in an in vitro Wayne model (6).”
BackgroundInfluentialThe Enduring Hypoxic Response of Mycobacterium tuberculosis
Rustad, T. R., Harrell, M. I., Liao, R., & Sherman, D. R. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001502 · Cited by 491 · cited 4×
“For example, DosR of M. tuberculosis H37Rv was shown not to be strictly required for survival of hypoxia in vitro (125).”
BackgroundInfluentialTuberculosis — metabolism and respiration in the absence of growth
Boshoff, H. I. M., & Barry, C. E. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1065 · Cited by 448 · cited 1×
“…c pathway consisting of a menaquinol-cytochrome c oxidoreductase termed the bc 1 complex (encoded by the qcrCAB operon, complex III) and an aa 3 -type cytochrome c oxidase (encoded by the genes ctaBCDE , complex IV) belonging to the heme-copper respiratory oxidase family (69 – 71) (Table 1).”
BackgroundVoskuil, M. I., Visconti, K. C., & Schoolnik, G. K. (2004) · Tuberculosis · doi:10.1016/j.tube.2004.02.003 · Cited by 448 · cited 2×
“In M. tuberculosis , cytochrome bd is upregulated in the early stages of NRP-1 (i.e., decreasing oxygen) (68), in NRP-2 (18), and in response to nitric oxide (NO) (18).”
BackgroundCyanobacterial hydrogenases: diversity, regulation and applications
Tamagnini, P., Leitão, E., Oliveira, P., Ferreira, D., Pinto, F., Harris, D. J., Heidorn, T., & Lindblad, P. (2007) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2007.00085.x · Cited by 367 · cited 1×
“Hyd1 aligns closely with group 2a uptake hydrogenases of the cyanobacteria such as Nostoc , indicating that it oxidizes H 2 (51).”
BackgroundDiarylquinolines Are Bactericidal for Dormant Mycobacteria as a Result of Disturbed ATP Homeostasis
Koul, A., Vranckx, L., Dendouga, N., Balemans, W., Van den Wyngaert, I., Vergauwen, K., Göhlmann, H. W. H., Willebrords, R., Poncelet, A., Guillemont, J., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803899200 · Cited by 364 · cited 2×
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F 1 F 0 -ATP synthase and inhibit ATP synthesis (109, 111, 112).”
BackgroundMycobacterium tuberculosis nuoG Is a Virulence Gene That Inhibits Apoptosis of Infected Host Cells
Velmurugan, K., Chen, B., Miller, J. L., Azogue, S., Gurses, S. A., Hsu, T., Glickman, M. S., Jacobs, W. R., Porcelli, S. A., & Briken, V. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030110 · Cited by 330 · cited 1×
“tuberculosis mutants lacking only one of the subunits of NDH-1, nuoG, have an in vivo phenotype, where this gene was critical for host macrophage apoptosis inhibition and mouse virulence (17).”
BackgroundMetabolic Regulation of Mycobacterial Growth and Antibiotic Sensitivity
Baek, S.-H., Li, A. H., & Sassetti, C. M. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001065 · Cited by 324 · cited 1×
“In contrast, in a TraSH screen selecting for mutants that continue to replicate under hypoxic conditions, Baek and coworkers (40) found SDH2 mutants overrepresented.”
BackgroundMolecular Biology of Microbial Hydrogenases
Vignais, P. M., & Colbeau, A. (2004) · Current Issues in Molecular Biology · doi:10.21775/cimb.006.159 · Cited by 320
Shi, L., Sohaskey, C. D., Kana, B. D., Dawes, S., North, R. J., Mizrahi, V., & Gennaro, M. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507850102 · Cited by 301 · cited 11×
“Intriguingly, mRNA levels of cydA increased transiently about 7-fold after 30 days in mouse lungs (18).”
BackgroundInfluentialInhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs
Weinstein, E. A., Yano, T., Li, L.-S., Avarbock, D., Avarbock, A., Helm, D., McColm, A. A., Duncan, K., Lonsdale, J. T., & Rubin, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500469102 · Cited by 289 · cited 7×
“M. tuberculosis harbors two copies of NDH-2 ( ndhRv1854c and ndhA Rv0392c ) (12) (Table 1), which are well conserved among slow-growing mycobacterial species.”
BackgroundMethodInfluentialAltered NADH/NAD + Ratio Mediates Coresistance to Isoniazid and Ethionamide in Mycobacteria
Vilchèze, C., Weisbrod, T. R., Chen, B., Kremer, L., Hazbón, M. H., Wang, F., Alland, D., Sacchettini, J. C., & Jacobs, W. R. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.2.708-720.2005 · Cited by 284 · cited 12×
“bovis were transformed with a replicative plasmid containing ndh, the ratio NAD/NADH doubled (15), further confirming the involvement of ndh in the oxidation of NADH into NAD.”
BackgroundInfluentialSelf-citationBerry, E. A., & Trumpower, B. L. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89576-x · Cited by 281 · cited 1×
“Supercomplexes between bc 1 and aa 3 have been reported for C. glutamicum (72), Paracoccus denitri fi cans (75), and thermophilic strain PS3 (76).”
BackgroundSuccinate dehydrogenase and fumarate reductase from Escherichia coli
Cecchini, G., Schröder, I., Gunsalus, R. P., & Maklashina, E. (2002) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(01)00238-9 · Cited by 279 · cited 1×
“Menaquinone has a lower midpoint redox potential (Em = −74 mV) compared to ubiquinone (Em = +113 mV) and is ideally poised to donate electrons to fumarate during anaerobic conditions (39).”
BackgroundEoh, H., & Rhee, K. Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219375110 · Cited by 278 · cited 3×
“A more recent study suggests that the glyoxylate shunt, and not the reverse TCA, is used tometabolize both glycolytic and fatty acid carbon sources in response to oxygen limitation, and this route also produces succinate as its metabolic end product (43).”
BackgroundInfluentialBIOCHEMICAL DIFFERENTIATION OF MYCOBACTERIUM TUBERCULOSIS GROWN IN VIVO AND IN VITRO
Segal, W., & Bloch, H. (1956) · Journal of Bacteriology · doi:10.1128/jb.72.2.132-141.1956 · Cited by 272
New Insights into Type II NAD(P)H:Quinone Oxidoreductases
Melo, A. M. P., Bandeiras, T. M., & Teixeira, M. S. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.4.603-616.2004 · Cited by 270 · cited 1×
“In some cases more than one copy is present (24).”
BackgroundRedundancy of aerobic respiratory chains in bacteria? Routes, reasons and regulation
Poole, R. K., & Cook, G. M. (2000) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(00)43005-5 · Cited by 258 · cited 2×
“Cyto-chrome bd mutants of E. coli have been shown to have a pleiotropic phenotype: they are sensitive to H 2 O 2 , nitric oxide, temperature, and iron (III) chelators and are unable to exit from stationary phase and resume aerobic growth at 37°C (77).”
BackgroundInfluentialSelf-citationFumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis
Watanabe, S., Zimmermann, M., Goodwin, M. B., Sauer, U., Barry, C. E., & Boshoff, H. I. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002287 · Cited by 246 · cited 1×
“tuberculosis grown under hypoxia metabolizes glucose through a reverse TCA cycle to generate succinate as an excreted fermentation end product (42).”
BackgroundD'mello, R., Hill, S., & Poole, R. K. (1996) · Microbiology · doi:10.1099/00221287-142-4-755 · Cited by 244
Smith, D. A., Parish, T., Stoker, N. G., & Bancroft, G. J. (2001) · Infection and Immunity · doi:10.1128/iai.69.2.1442-1150.2001 · Cited by 243 · cited 1×
“Interest-ingly, a proC mutant of M. tuberculosis was avirulent in immunocompetent mice, but this was not due to its inability to proliferate intracellulary because bacterial loads increased in the mouse lungs after 20 days postin-fection (49).”
BackgroundGlobal Assessment of Genomic Regions Required for Growth in Mycobacterium tuberculosis
Zhang, Y. J., Ioerger, T. R., Huttenhower, C., Long, J. E., Sassetti, C. M., Sacchettini, J. C., & Rubin, E. J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002946 · Cited by 242
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“…of the transcriptional machinery in mycobacteria may be supported by the fi nding that WhiB3 interacts with the major sigma factor, SigA (RpoV) (124), but the effect of this interaction on SigA activity is not known, and further study is required to understand the precise role of WhiB3 in…”
BackgroundUnique Flexibility in Energy Metabolism Allows Mycobacteria to Combat Starvation and Hypoxia
Berney, M., & Cook, G. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008614 · Cited by 235 · cited 10×
“Rather, increased expression (15-fold) of the nuo operon in M. smegmatis was observed in a carbon-limited chemostat in response to a slowdown in growth rate (16).”
BackgroundInfluentialSelf-citationRickman, L., Scott, C. S., Hunt, D. M., Hutchinson, T., Menendez, M. C., Whalan, R. H., Hinds, J., Colston, M. J., Green, J. D., & Buxton, R. S. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04609.x · Cited by 226
Heme Oxygenase-1-derived Carbon Monoxide Induces the Mycobacterium tuberculosis Dormancy Regulon
Kumar, A., Deshane, J. S., Crossman, D. K., Bolisetty, S., Yan, B., Kramnik, I., Agarwal, A., & Steyn, A. J. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802274200 · Cited by 218 · cited 2×
“In addition to hypoxia, the Dos-regulon has also been shown to be activated by exposure of M. tuberculosis to NO or CO (88, 90, 120).”
BackgroundMycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection
Shiloh, M. U., Manzanillo, P. S., & Cox, J. S. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.03.007 · Cited by 217 · cited 1×
“In addition to hypoxia, the Dos-regulon has also been shown to be activated by exposure of M. tuberculosis to NO or CO (88, 90, 120).”
BackgroundHuitric, E., Verhasselt, P., Koul, A., Andries, K., Hoffner, S. E., & Andersson, D. I. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01611-09 · Cited by 216 · cited 1×
“Genome sequencing of both M. tuberculosis and M. smegmatis mutants that are resistant to diarylquinolines (i.e., TMC207) revealed that the target of these compounds is the oligomeric c ring (encoded by atpE ) of the enzyme (109, 113, 114).”
BackgroundOrdway, D. J., Viveiros, M., Leandro, C., Bettencourt, R., Almeida, J. M. D. N., Martins, M., Kristiansen, J. E., Molnar, J. A., & Amaral, L. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.917-922.2003 · Cited by 201 · cited 1×
“Despite poor in vitro activity, drugs of the phenothiazine family (tri fl uoroperazine, chlor-promazine) have potent activity in vitro against drug-susceptible and drug-resistant M. tuberculosis strains (34, 35).”
BackgroundTian, J., Bryk, R., Itoh, M., Suematsu, M., & Nathan, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501605102 · Cited by 200 · cited 1×
“Succinate dehydrogenase activity has been measured in M. tuberculosis as well as many other mycobacterial species (37, 38), but it is still unclear which of the three enzymes, or all, are responsible for this activity.”
BackgroundSingh, A., Guidry, L., Narasimhulu, K. V., Mai, D., Trombley, J., Redding, K. E., Giles, G. I., Lancaster, J. R., & Steyn, A. J. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700490104 · Cited by 194 · cited 5×
“The genome of M. tuberculosis also lacks orthologs of transcription regulator FNR which, in combination with NarL, are responsible for the transcriptional activation of the narGHJI operon by anaerobic conditions in E. coli (21).”
BackgroundInfluentialThe effects of reactive nitrogen intermediates on gene expression inMycobacterium tuberculosis
Ohno, H., Zhu, G., Mohan, V. P., Chu, D., Kohno, S., Jacobs, W. R., & Chan, J. (2003) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00307.x · Cited by 190
Role of narK2X and narGHJI inHypoxic Upregulation of Nitrate Reduction by Mycobacteriumtuberculosis
Sohaskey, C. D., & Wayne, L. G. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.24.7247-7256.2003 · Cited by 188 · cited 4×
“Importantly, however, the expression of the narGHJI operon in M. tuberculosis is not upregulated in response to either hypoxia or stationary phase ( 85).”
BackgroundInfluentialA Bacterial Glutathione Transporter (Escherichia coli CydDC) Exports Reductant to the Periplasm
Pittman, M. S., Robinson, H. C., & Poole, R. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503075200 · Cited by 185 · cited 1×
“In E. coli , the CydDC protein (ABC transporter) has been reported to pump glutathione and cysteine into the periplasm to maintain redox homeostasis (80).”
BackgroundNiebisch, A., & Bott, M. (2001) · Archives of Microbiology · doi:10.1007/s002030100262 · Cited by 182
Global Transcriptional Profile of Mycobacterium tuberculosis during THP-1 Human Macrophage Infection
Fontán, P. A., Aris, V. M., Ghanny, S., Soteropoulos, P., & Smith, I. (2007) · Infection and Immunity · doi:10.1128/iai.00974-07 · Cited by 180 · cited 1×
“, Rv0082 to Rv0087) and is upregulated during infection of human macrophage-like THP-1 cells (95).”
BackgroundNitrate and nitrite transport in bacteria
MOIR, J. W. B., & Wood, N. J. (2001) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000849 · Cited by 178 · cited 1×
“Inhibition of nitrate transport by oxygen has been documented in other bacteria (87).”
BackgroundUnique Rotary ATP Synthase and Its Biological Diversity
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Self-citationIdentification of Novel Imidazo[1,2-a]pyridine Inhibitors Targeting M. tuberculosis QcrB
Abrahams, K. A., Cox, J. A. G., Spivey, V. L., Loman, N. J., Pallen, M. J., Constantinidou, C., Fernández, R., Alemparte, C., Remuiñán, M. J., Barros, D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052951 · Cited by 177 · cited 1×
“The QcrB subunit has been recently shown to be the target of novel imidazo[1,2-a ]pyridine inhibitors that are active against M. tuberculosis at low micromolar concentrations (73).”
BackgroundIn Vitro Antimycobacterial Spectrum of a Diarylquinoline ATP Synthase Inhibitor
Huitric, E., Verhasselt, P., Andries, K., & Hoffner, S. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00181-07 · Cited by 173 · cited 1×
“Genome sequencing of both M. tuberculosis and M. smegmatis mutants that are resistant to diarylquinolines (i.e., TMC207) revealed that the target of these compounds is the oligomeric c ring (encoded by atpE ) of the enzyme (109, 113, 114).”
BackgroundConstant, P., Chowdhury, S. P., Pratscher, J., & Conrad, R. (2010) · Environmental Microbiology · doi:10.1111/j.1462-2920.2009.02130.x · Cited by 171
Miesel, L., Weisbrod, T. R., Marcinkeviciene, J. A., Bittman, R., & Jacobs, W. R. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.9.2459-2467.1998 · Cited by 155 · cited 7×
“The correlation between ndh mutations and serine/glycine auxotrophy was attributed to the increase in NADH concentration, which might inhibit the first step in serine/glycine biosynthesis (14).”
BackgroundInfluentialStructural biology of proline catabolism
Tanner, J. J. (2008) · Amino Acids · doi:10.1007/s00726-008-0062-5 · Cited by 154 · cited 3×
“Proline dehydrogenase is upregulated under both energy-limiting conditions and hypoxia (7, 16) and is increasingly being recognized as a critical amino acid in cellular bioenergetics and redox control (46).”
BackgroundCharacterization of the cydAB -Encoded Cytochrome bd Oxidase from Mycobacterium smegmatis
Kana, B. D., Weinstein, E. A., Avarbock, D., Dawes, S. S., Rubin, H., & Mizrahi, V. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.24.7076-7086.2001 · Cited by 153
Yano, T., Li, L.-S., Weinstein, E., Teh, J.-S., & Rubin, H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508844200 · Cited by 150 · cited 3×
“, phenothiazine analogues, platanetin, quinolinyl pyrimidines) (12, 27, 33), but the mechanism of inhibition remains unknown.”
BackgroundIntracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG
Rao, M., Streur, T. L., Aldwell, F. E., & Cook, G. M. (2001) · Microbiology · doi:10.1099/00221287-147-4-1017 · Cited by 148 · cited 2×
“As the pH of the growth medium changes and becomes mildly acidic, mycobacteria are able to generate a considerable transmembrane pH gradient (Z Δ pH) and maintain a constant PMF (4).”
BackgroundSelf-citationMechanism of Oxygen Sensing by the Bacterial Transcription Factor Fumarate-Nitrate Reduction (FNR)
Crack, J. C., Green, J. D., & THOMSON, A. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309878200 · Cited by 147 · cited 1×
“Furthermore, in the presence of oxygen, the WhiB3 [4Fe-4S] 2+ cluster is degraded fi rst to a [3Fe-4S] + cluster, then a [2Fe-2S] 2+ cluster and subsequently lost altogether, in a mechanism reminiscent of the one found in the E. coli oxygen sensor FNR (121, 122).”
BackgroundDhiman, R. K., Mahapatra, S., Slayden, R. A., Boyne, M. E., Lenaerts, A., Hinshaw, J. C., Angala, S. K., Chatterjee, D., Biswas, K., Narayanasamy, P., et al. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06625.x · Cited by 146 · cited 1×
“Several new antitubercular compounds have been reported that target oxidative phosphorylation in mycobacteria (12, 109, 110).”
BackgroundMolenaar, D., van der Rest, M. E., Drysch, A., & Yücel, R. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.24.6884-6891.2000 · Cited by 143 · cited 3×
“The membrane-associated malate quinone oxidore-ductase (MQO) oxidizes malate to oxaloacetate and transfers the reducing equivalents to menaquinone (59, 60) (Fig.”
BackgroundMethodAerobic respiratory chain of Escherichia coli is not allowed to work in fully uncoupled mode
Borisov, V. B., Murali, R., Verkhovskaya, M. L., Bloch, D. A., Han, H., Gennis, R. B., & Verkhovsky, M. I. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108217108 · Cited by 143 · cited 1×
“The existence of two cytochrome bd -type oxidases (I and II) is not unprecedented in bacteria (77), and recent work has reported that cytochrome bd -II in E. coli is able to generate a PMF with a H + /e − ratio of 1.0 (78).”
BackgroundInfluentialProbing the Interaction of the Diarylquinoline TMC207 with Its Target Mycobacterial ATP Synthase
Haagsma, A. C., Podasca, I., Koul, A., Andries, K., Guillemont, J., Lill, H., & Bald, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023575 · Cited by 141 · cited 2×
“Further investigations with inverted membrane vesicles of M. smegmatis and TMC207 have revealed that TMC207 acts independently of the PMF and that electrostatic forces play an important role in the interaction of the drug with the ATP synthase (116).”
BackgroundAmaral, L., Kristiansen, J. E., Abebe, L. S., & Millett, W. P. (1996) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/38.6.1049 · Cited by 138 · cited 1×
“Despite poor in vitro activity, drugs of the phenothiazine family (tri fl uoroperazine, chlor-promazine) have potent activity in vitro against drug-susceptible and drug-resistant M. tuberculosis strains (34, 35).”
BackgroundBacon, J., James, B. W., Wernisch, L., Williams, A., Morley, K. A., Hatch, G. J., Mangan, J. A., Hinds, J., Stoker, N. G., Butcher, P. D., et al. (2004) · Tuberculosis · doi:10.1016/j.tube.2003.12.011 · Cited by 137 · cited 2×
“Increased expression of this operon has been shown during carbon starvation (20), oxygen depletion (44), and in macrophages (19), suggesting a role for this enzyme in persistence.”
BackgroundMatsoso, L. G., Kana, B. D., Crellin, P. K., Lea-Smith, D. J., Pelosi, A., Powell, D., Dawes, S. S., Rubin, H., Coppel, R. L., & Mizrahi, V. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.18.6300-6308.2005 · Cited by 134
Structural insight into the type-II mitochondrial NADH dehydrogenases
Feng, Y., Li, W., Li, J., Wang, J., Ge, J., Xu, D., Liu, Y., Wu, K., Zeng, Q., Wu, J., et al. (2012) · Nature · doi:10.1038/nature11541 · Cited by 133 · cited 1×
“No tertiary structural information exists for either the bacterial, plant, or protist NDH-2 enzymes, but the yeast NDH-2 structure was recently solved by two laboratories (22, 23).”
BackgroundBiagini, G. A., Viriyavejakul, P., O’Neill, P. M., Bray, P. G., & Ward, S. A. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.5.1841-1851.2006 · Cited by 132 · cited 1×
“NDH-2 has not been reported in mammalian mitochondria, leading to the proposal that these enzymes may represent a potential drug target for the treatment of human pathogens (6, 12, 27, 30, 31) and intracellular parasites (32).”
BackgroundCotter, P. A., Melville, S. B., Albrecht, J. A., & Gunsalus, R. P. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.5031860.x · Cited by 130
Unden, G., & Schirawski, J. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.4731841.x · Cited by 130 · cited 1×
“coli requires complex I, and expression of the nuo operon is stimulated by the presence of fumarate (41).”
BackgroundMcAdam, R. A., Quan, S., Smith, D. A., Bardarov, S., Betts, J. C., Cook, F. C., Hooker, E. U., Lewis, A. P., Woollard, P., Everett, M. J., et al. (2002) · Microbiology · doi:10.1099/00221287-148-10-2975 · Cited by 128
The Three Families of Respiratory NADH Dehydrogenases
Kerscher, S., Dröse, S., Zickermann, V., & Brandt, U. (2007) · Results and Problems in Cell Differentiation · doi:10.1007/400_2007_028 · Cited by 127 · cited 1×
“In bacteria, three different types of respiratory NADH dehydrogenases have been identified and characterized on the basis of reaction mechanism, subunit composition, and protein architecture (11).”
BackgroundClegg, S. J., Yu, F., Griffiths, L., & Cole, J. A. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02858.x · Cited by 124
de Jonge, M. R., Koymans, L. M. H., Guillemont, J., Koul, A., & Andries, K. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21376 · Cited by 124 · cited 1×
“The puri fi ed c ring from M. smegmatis binds TMC207 with a K D of 500 nm, and modeling/docking and kinetic studies suggest that TMC207 blocks rotary movement of the c ring during catalysis by mimicking key residues in the proton transfer chain (115, 116).”
BackgroundMycobacterium tuberculosis persistence mutants identified by screening in isoniazid-treated mice
Dhar, N., & McKinney, J. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003219107 · Cited by 123 · cited 1×
“A cydC mutant of M. tuberculosis showed reduced ability to survive the transition from acute to chronic infection in mice (18), and Dhar and McKinney have reported that CydC plays a role in mycobacterial persistence in INH-treated mice (81).”
BackgroundSone, N., SEKIMACHI, M., & Kutoh, E. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47736-8 · Cited by 122 · cited 1×
“Supercomplexes between bc 1 and aa 3 have been reported for C. glutamicum (72), Paracoccus denitri fi cans (75), and thermophilic strain PS3 (76).”
BackgroundBacillus subtilis F0F1 ATPase: DNA sequence of the atp operon and characterization of atp mutants
Santana, M. M., Ionescu, M., Vertès, A. A., Longin, R., Kunst, F., Danchin, A., & Glaser, P. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.22.6802-6811.1994 · Cited by 122
Niebisch, A., & Bott, M. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210499200 · Cited by 120
A missing link between complex I and group 4 membrane-bound [NiFe] hydrogenases
Marreiros, B. C., Batista, A. P., Duarte, A. M. S., & Pereira, M. M. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.09.012 · Cited by 120
The F 1 F o -ATP Synthase of Mycobacterium smegmatis Is Essential for Growth
Tran, S. L., & Cook, G. M. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.14.5023-5028.2005 · Cited by 116
Self-citationIwata, M., Lee, Y., Yamashita, T., Yagi, T., Iwata, S., Cameron, A. D., & Maher, M. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210059109 · Cited by 112 · cited 1×
“No tertiary structural information exists for either the bacterial, plant, or protist NDH-2 enzymes, but the yeast NDH-2 structure was recently solved by two laboratories (22, 23).”
BackgroundNitrate Enhances the Survival of Mycobacterium tuberculosis during Inhibition of Respiration
Sohaskey, C. D. (2008) · Journal of Bacteriology · doi:10.1128/jb.01857-07 · Cited by 108 · cited 1×
“Sohaskey (91) has reported that exogenously supplied nitrate has no effect on long-term persistence during gradual oxygen depletion but played an important role during rapid adaptation to hypoxia ( 18 h).”
BackgroundMolenaar, D., van der Rest, M. E., & Petrović, S. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2540395.x · Cited by 105 · cited 2×
“The membrane-associated malate quinone oxidore-ductase (MQO) oxidizes malate to oxaloacetate and transfers the reducing equivalents to menaquinone (59, 60) (Fig.”
BackgroundMethodConstant, P., Chowdhury, S. P., Hesse, L., Pratscher, J., & Conrad, R. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.00673-11 · Cited by 105 · cited 2×
“These data suggest that Hyd2 oxidizes hydrogen at very low concentrations, which fi ts with its purported role as a high-af fi nity hydrogenase (52).”
BackgroundHaagsma, A. C., Driessen, N. N., Hahn, M., Lill, H., & Bald, D. (2010) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2010.02123.x · Cited by 102 · cited 2×
“smegmatis demonstrate latent ATPase activity that could be activated by methanol and the PMF, suggesting regulation by the epsilon subunit and ADP inhibition (9).”
BackgroundTan, M. P., de Sequeira, P. C., Lin, W. W., Phong, W. Y., Cliff, P. R., Ng, S. H., Lee, B. H., Camacho, L. R., Schnappinger, D., Ehrt, S., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013356 · Cited by 99 · cited 3×
“The nirBD genes are operonic and nonessential for growth, and unlike the narGHJI genes, no role in resistance to acid stress under hypoxia was noted for NirBD (92).”
BackgroundInfluentialGoldman, B. S., Gabbert, K. K., & Kranz, R. G. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.21.6348-6351.1996 · Cited by 97 · cited 1×
“In E. coli , cydAB and cydDC form two discrete operons, c ydDC mutants are defective in cytochrome bd assembly, and the periplasmic space is more oxidized in the mutant versus wild type (79).”
BackgroundQuinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents
Shirude, P. S., Paul, B., Choudhury, N. R., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300134b · Cited by 97 · cited 1×
“, phenothiazine analogues, platanetin, quinolinyl pyrimidines) (12, 27, 33), but the mechanism of inhibition remains unknown.”
BackgroundGrowth of Mycobacteria on Carbon Monoxide and Methanol
Park, S. W., Hwang, E. H., Park, H., Kim, J. A., Heo, J., Lee, K. H., Song, T., Kim, E., Ro, Y. T., Kim, S. W., et al. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.1.142-147.2003 · Cited by 94 · cited 1×
“It has been shown that M. tuberculosis H37Ra, which possesses CO-DH activity, can grow on CO as a sole source of carbon and fuel for energy generation (56) (Fig.”
BackgroundUptake ofCarbon Monoxide and Hydrogen at Environmentally Relevant Concentrationsby Mycobacteria†
King, G. M. (2003) · Applied and Environmental Microbiology · doi:10.1128/aem.69.12.7266-7272.2003 · Cited by 93 · cited 1×
“It has been shown that M. smegmatis , among other mycobacterial species, can oxidize molecular hydrogen in the presence of carbon monoxide (CO), implying that M. smegmatis expresses a functional hydrogenase (54).”
BackgroundMenzel, R., & Roth, J. R. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68828-9 · Cited by 91
Nark is a nitrite‐extrusion system involved in anaerobic nitrate respiration by Escherichia coli
Rowe, J. J., Ubbink-Kok, T., Douwe Molenaar, B., Konings, W. N., & Driessen, A. J. M. (1994) · Molecular Microbiology · doi:10.1111/j.1365-2958.1994.tb01044.x · Cited by 89
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“Glycerol-3-phosphate dehydrogenase catalyzes the oxidation of glycerol-3-phosphate to dihydroxy-acetone phosphate and reduces either quinone or NADP (57).”
BackgroundFriedl, P., Hoppe, J., Gunsalus, R. P., Michelsen, O., von Meyenburg, K., & Schairer, H. U. (1983) · The EMBO Journal · doi:10.1002/j.1460-2075.1983.tb01388.x · Cited by 87 · cited 1×
“In other bacteria, the F 1 F 0 -ATP synthase is dispensable for growth on fermentable carbon sources (104, 105), where increased glycolytic fl ux can compensate for the loss of oxidative phosphorylation.”
BackgroundThe hydrogenases of Geobacter sulfurreducens: a comparative genomic perspective
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“Upon closer inspection, the predicted [NiFe]-hydrogenase of M. tuberculosis appears to form part of an Ehr (Ech hydrogenase-related) complex (99, 100).”
BackgroundEvidence for a cytochrome bcc–aa 3 interaction in the respiratory chain of Mycobacterium smegmatis
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BackgroundBacterial Na+- or H+-coupled ATP Synthases Operating at Low Electrochemical Potential
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Self-citationToxin-Antitoxin Systems of Mycobacterium smegmatis Are Essential for Cell Survival
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“TMC207 is bactericidal toward most species of mycobacteria (109) but is only bacteriostatic against M. avium (118) and M. smegmatis (M. Berney and G. M. Cook, unpublished data).”
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BackgroundInfluentialSulfite Reduction in Mycobacteria
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“Without OXPHOS, ATP levels decline, relieving carbon catabolism and the TCA cycle of feedback inhibition.”
InfluentialBactericidal mode of action of bedaquiline
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“tuberculosis produces energy via oxidative phosphorylation.(211) The cytochrome bcc complex (also referred to as cytochrome bc1 complex) is a component of electron transport chain of M.”
Background
Metadata
- Authors
- Cook, G. M., Hards, K., Vilchèze, C., Hartman, T., & Berney, M.
- Affiliations
- University of Otago (NZ)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Cook, Gregory M.
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2014-05-02
- Volume
- 2
- Issue
- 3
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC4205543
- OpenAlex
- W2001454891
- Cited by
- 212
- References
- 130
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 15 · 2023: 15 · 2022: 22 · 2021: 24 · 2020: 25 · 2019: 22 · 2018: 16 · 2017: 15 · 2016: 6 · 2015: 7 · 2014: 3
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology Spectrum (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Inha University
- Maurice Wilkins Centre for Molecular Biodiscovery
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI026170, AI-26170, R37AI026170)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- mycobacteria, Mycobacterium tuberculosis, bacterial respiration, oxidative phosphorylation, electron transport chain, cytochrome c oxidase, F1FO-ATP synthase, proton motive force, hypoxia, anaerobic metabolism, reductase, hydrogenase, ferredoxin, respiratory inhibitors, tuberculosis drug targets
- MeSH terms
- Adenosine Triphosphate, Aerobiosis, Energy Metabolism, Mycobacterium tuberculosis, Oxidative Phosphorylation, Oxidoreductases, Metabolic Networks and Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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