An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence
Open accessAbstract
It was demonstrated previously that abrupt transfer of vigorously aerated cultures of Mycobacterium tuberculosis to anaerobic conditions resulted in their rapid death, but gradual depletion of available O2 permitted expression of increased tolerance to anaerobiosis. Those studies used a model based on adaptation of unagitated bacilli as they settled through a self-generated O2 gradient, but the model did not permit examination of homogeneous populations of bacilli during discrete stages in that adaptation. The present report describes a model based on culture of tubercle bacilli in deep liquid medium with very gentle stirring that keeps them in uniform dispersion while controlling the rate at which O2 is depleted. In this model, at least two stages of nonreplicating persistence were seen. The shift into first stage, designated NRP stage 1, occurred abruptly at a point when the declining dissolved O2 level approached 1% saturation. This microaerophilic stage was characterized by a slow rate of increase in turbidity without a corresponding increase in numbers of CFU or synthesis of DNA. However, a high rate of production of glycine dehydrogenase was initiated and sustained while the bacilli were in this state, and a steady ATP concentration was maintained. When the dissolved O2 content of the culture dropped below about 0.06% saturation, the bacilli shifted down abruptly to an anaerobic stage, designated NRP stage 2, in which no further increase in turbidity was seen and the co…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
We can learn about these states from chronic stage mouse experiments and from in vitro experiments in starvation, late stationary phase and oxygen deprivation, during which growth stasis is observed.
“We can learn about these states from chronic stage mouse experiments48 and from in vitro experiments in starvation, late stationary phase and oxygen deprivation49, during which growth stasis is observed.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [49]
Cited by
Sorted by citations
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 · see citing works
Nonreplicating Persistence of <i>Mycobacterium</i> <i>Tuberculosis</i>
Wayne, L. G., & Sohaskey, C. D. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.139 · Cited by 807 · see citing works
Self-citationPark, 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 · see citing works
Rao, 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 · see citing works
The 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 · see citing works
Voskuil, M. I., Visconti, K. C., & Schoolnik, G. K. (2004) · Tuberculosis · doi:10.1016/j.tube.2004.02.003 · Cited by 448 · see citing works
Tuberculosis — 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 · see citing works
Bacterial Growth and Cell Division: a Mycobacterial Perspective
Hett, E. C., & Rubin, E. J. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00028-07 · Cited by 408 · see citing works
The mycobacterial cell envelope — a moving target
Dulberger, C. L., Rubin, E. J., & Boutte, C. C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0273-7 · Cited by 365 · see citing works
Diarylquinolines 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 · see citing works
Metabolic 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 · see citing works
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 · see citing works
Kang, C.-M., Nyayapathy, S., Lee, J.-Y., Suh, J.-W., & Husson, R. N. (2008) · Microbiology · doi:10.1099/mic.0.2007/014076-0 · Cited by 264 · see citing works
Fumarate 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 · see citing works
Unique 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 · see citing works
Sohaskey, C. D., & Wayne, L. G. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.24.7247-7256.2003 · Cited by 188 · see citing works
Self-citationKana, 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 · see citing works
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 · see citing works
Dhiman, 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 · see citing works
Nitrate Enhances the Survival of <i>Mycobacterium tuberculosis</i> during Inhibition of Respiration
Sohaskey, C. D. (2008) · Journal of Bacteriology · doi:10.1128/jb.01857-07 · Cited by 108 · see citing works
Uptake 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 · see citing works
Bacon, J., Alderwick, L. J., Allnutt, J. A., Gabasova, E., Watson, R., Hatch, K. A., Clark, S. O., Jeeves, R. E., Marriott, A., Rayner, E., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087329 · Cited by 74 · see citing works
Dziadek, J., Madiraju, M. V. V. S., Rutherford, S. A., Atkinson, M. A. L., & Rajagopalan, M. (2002) · Microbiology · doi:10.1099/00221287-148-4-961 · Cited by 63 · see citing works
Regulation of nitrate reductase activity in Mycobacterium tuberculosis by oxygen and nitric oxide
Sohaskey, C. D. (2005) · Microbiology · doi:10.1099/mic.0.28263-0 · Cited by 60 · see citing works
A methoxylated flavone from <i>Artemisia afra</i> kills <i>Mycobacterium tuberculosis</i>
Kellogg, J. J., Alonso, M. N., Jordan, R. T., Xiao, J., Cafiero, J. H., Bush, T., Towler, M., Weathers, P., & Shell, S. S. (2023) · doi:10.1101/2023.10.11.561885 · Cited by 3 · see citing works
- Authors
- Wayne, L. G., & Hayes, L. G.
- Affiliations
- Veterans Health Administration (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1996-06
- Volume
- 64
- Issue
- 6
- Pages
- 2062-2069
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC174037
- OpenAlex
- W2123084649
- Cited by
- 1,141
- References
- 0
- Citations by year
- 2026: 34 · 2025: 30 · 2024: 32 · 2023: 40 · 2022: 45 · 2021: 45 · 2020: 44 · 2019: 56 · 2018: 48 · 2017: 60 · 2016: 62 · 2015: 57 · 2014: 56 · 2013: 58 · 2012: 63
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- Mycobacterium tuberculosis, anaerobic survival, oxygen depletion, ATP maintenance, dormancy, drug sensitivity, in vitro culture model, tuberculosis reactivation, antimicrobial mechanisms, DNA synthesis inhibition
- MeSH terms
- Adenosine Triphosphate, Amino Acid Oxidoreductases, DNA, Bacterial, Mycobacterium tuberculosis, Oxygen, Glycine Dehydrogenase
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
