Dual function of Candida auris mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host
Open accessAbstract
Screen of mutants from a mannosyltransferase family identified the importance of MNT5 for C. auris biofilm drug resistance and neutrophil evasion. Biochemical analysis of the mnt5∆ mutant matrix and cell wall identified alterations in the mannan structures. Resistance and matrix for mnt5∆ were restored with delivery of wild-type matrix via extracellular vesicles. Analysis of the mnt5 ∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for MNT5 in mannan masking of pathogen-associated molecular patterns. IMPORTANCE: C. auris recalcitrance is linked to biofilm drug resistance and immune evasion. The mannosyltransferase encoded by MNT5 is necessary for both phenotypes and may serve as a useful therapeutic target.
AI snapshot
Written from the paper’s full text.
TL;DR
The Candida auris mannosyltransferase MNT5 is required for biofilm matrix function and cell wall mannan masking, protecting biofilms from fluconazole and limiting neutrophil engagement. Wild-type extracellular vesicles restore the mnt5∆ biofilm drug-resistance and matrix phenotypes, while MNT5 loss exposes β-glucan and chitin PAMPs.
Key findings
- Disruption of MNT5 increased fluconazole killing of C. auris biofilms by more than twofold versus wild type; genetic complementation restored resistance, and exogenous wild-type EVs returned the mnt5∆ phenotype toward wild-type, whereas mnt5∆ EVs did not.
- The mnt5∆ biofilm matrix showed a marked reduction in encasing extracellular matrix by SEM and altered glycan composition by NMR: mannan residues were 97.7% in mnt5∆ versus 92.6% in wild type, while β-glucan was 2.3% versus 7.4%.
- Neutrophils engaged the mnt5∆ mutant at a greater than threefold higher rate than wild type; complementation restored evasion, and other MNT mutants did not show this change.
- The mnt5∆ cell wall had lower mannan (7.5% versus 20.5%) and higher glucan (92.4% versus 79.5%), with increased surface β-glucan and chitin exposure—over 12-fold and 6-fold greater than wild type, respectively.
Methods
- Screened a family of six C. auris mannosyltransferase mutants (MNT1, MNT2, MNT3, MNT4, MNT4b, MNT5) for biofilm growth and fluconazole susceptibility during biofilm formation, using 1000 µg/mL fluconazole and genetic complementation.
- Characterized biofilm matrix and cell wall polysaccharides by scanning electron microscopy, transmission electron microscopy, 1D 1H NMR, and 2D 1H-1H COSY, and tested EV add-back with wild-type or mnt5∆ EVs.
- Assessed host interaction by human neutrophil co-culture and measured surface PAMPs by immunofluorescence with Fc:dectin-1 for β-glucan and WGA-FITC for chitin; statistics included Kruskal–Wallis with Dunn’s test and two-tailed unpaired t-tests.
Limitations
- The paper states that MNT5 did not impact fungal growth or fitness in a mouse infection model (not shown), but the mouse infection data are not presented in the text.
- Several key controls or results are described as “not shown,” including growth defects and planktonic MICs to fluconazole, limiting independent assessment of those claims.
- Evident from the text: the mechanistic link between altered α-mannan structure and matrix deposition/PAMP masking is speculative, and the work relies heavily on in vitro biofilm, NMR, microscopy, and neutrophil co-culture systems rather than in vivo virulence detail.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
29 of 40 cited sources checked · 8 supported · 1 flagged · accuracy not yet measured
- Premisecitation
In the biofilm community, a unique extracellular mannan-glucan complex prevents antifungal drugs from reaching intracellular drug targets.
“In the biofilm community, a unique extracellular mannan-glucan complex has been shown to prevent antifungal drugs from reaching intracellular drug targets (17–20).”
Quote in the paperSubstantial claim3 of 4 sources checked- cites [17] Dominguez E, Zarnowski R, Sanchez H, Covelli AS, Westler WM, Azadi P, Nett J, Mitchell AP, Andes DR. 2018. Conservation and divergence in the Candida species biofilm matrix mannan-glucan complex structure, function, and genetic control. MBio 9: e00451-18. doi: 10.1128/mBio.00451-18 29615504 PMC5885036 source
- cites [18] Dominguez EG, Zarnowski R, Choy HL, Zhao M, Sanchez H, Nett JE, Andes DR. 2019. Conserved role for biofilm matrix polysaccharides in Candida auris drug resistance. mSphere 4: e00680-18. doi: 10.1128/mSphereDirect.00680-18 30602527 PMC6315084 source
- cites [19] Zarnowski R, Westler WM, Lacmbouh GA, Marita JM, Bothe JR, Bernhardt J, Lounes-Hadj Sahraoui A, Fontaine J, Sanchez H, Hatfield RD, Ntambi JM, Nett JE, Mitchell AP, Andes DR. 2014. Novel entries in a fungal biofilm matrix encyclopedia. MBio 5: e01333– 14. doi: 10.1128/mBio.01333-14 25096878 PMC4128356 source
The Results sections identify an extracellular mannan–glucan complex and show that removing some biofilm matrix increased intracellular fluconazole by 30%. But the Functional matrix analysis does not establish that the complex itself blocks drug entry: purified carbohydrate fractions did not reproduce the drug interaction seen with the whole matrix. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [20] Mitchell KF, Zarnowski R, Sanchez H, Edward JA, Reinicke EL, Nett JE, Mitchell AP, Andes DR. 2015. Community participation in biofilm matrix assembly and function. Proc Natl Acad Sci U S A 112: 4092– 4097. doi: 10.1073/pnas.1421437112 25770218 PMC4386410 source
- Premisecitation
Cell wall and extracellular matrix polysaccharides have mechanistic roles implicated in protection of Candida species from host response and drug therapies.
“Cell wall and extracellular matrix polysaccharides have mechanistic roles implicated in the protection of Candida species from host response and drug therapies (13–16).”
Quote in the paperSubstantial claim3 of 4 sources checked- cites [13] Buurman ET, Westwater C, Hube B, Brown AJ, Odds FC, Gow NA. 1998. Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. Proc Natl Acad Sci U S A 95: 7670– 7675. doi: 10.1073/pnas.95.13.7670 9636208 PMC22718 source
- cites [14] Hall RA, Bates S, Lenardon MD, Maccallum DM, Wagener J, Lowman DW, Kruppa MD, Williams DL, Odds FC, Brown AJP, Gow NAR. 2013. The Mnn2 mannosyltransferase family modulates mannoprotein fibril length, immune recognition and virulence of Candida albicans. PLoS Pathog 9: e1003276. doi: 10.1371/journal.ppat.1003276 23633946 PMC3636026 source
The Discussion (page not provided) describes cell-wall N-mannan as a shield that masks a pro-inflammatory β-glucan layer and links increased β-glucan exposure to enhanced macrophage recognition. This supports a mechanism involving protection from the host response in C. albicans, but the paper does not establish the claimed roles for extracellular-matrix polysaccharides, protection from drug therapies, or Candida species generally. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [15] Munro CA, Bates S, Buurman ET, Hughes HB, Maccallum DM, Bertram G, Atrih A, Ferguson MAJ, Bain JM, Brand A, Hamilton S, Westwater C, Thomson LM, Brown AJP, Odds FC, Gow NAR. 2005. Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence. J Biol Chem 280: 1051– 1060. doi: 10.1074/jbc.M411413200 15519997 PMC3749086 source
The introduction (indexed under Abstract; page unavailable) says C. albicans cell-wall components participate in host-response immunomodulation and adhesion, supporting a role in host interactions. The Results section on wall-damaging agents reports sensitivity to laboratory inhibitors, not protection from drug therapies. The paper does not establish a protective role for extracellular-matrix polysaccharides, and its findings concern C. albicans rather than Candida species generally. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [16] Díaz-Jiménez DF, Mora-Montes HM, Hernández-Cervantes A, Luna-Arias JP, Gow NAR, Flores-Carreón A. 2012. Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis. Biochem Biophys Res Commun 419: 77– 82. doi: 10.1016/j.bbrc.2012.01.131 22326920 PMC3480643 source
The Introduction (page unavailable) says C. albicans cell-wall polysaccharides contribute to a protective structure, that mannosylation affects recognition by the host innate immune system, and that disrupting certain mannosyltransferases increases antibiotic sensitivity. It does not address extracellular-matrix polysaccharides or establish protection from host responses and drug therapies across Candida species. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
Cell wall mannan masks immunostimulatory cell wall components preventing host cell recognition.
“Similarly, cell wall mannan masks immunostimulatory cell wall components preventing host cell recognition (15, 21).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [15] Munro CA, Bates S, Buurman ET, Hughes HB, Maccallum DM, Bertram G, Atrih A, Ferguson MAJ, Bain JM, Brand A, Hamilton S, Westwater C, Thomson LM, Brown AJP, Odds FC, Gow NAR. 2005. Mnt1p and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and virulence. J Biol Chem 280: 1051– 1060. doi: 10.1074/jbc.M411413200 15519997 PMC3749086 source
The introductory passage (labeled Abstract in our copy; page unavailable) says the outer cell-wall layer is enriched in mannoproteins and that the cell surface participates in immunomodulation. Neither that passage nor the Discussion passages say that mannan masks immunostimulatory components or prevents host-cell recognition; searches for masking and immune recognition found no such statement. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [21] Johnson CJ, Davis JM, Huttenlocher A, Kernien JF, Nett JE. 2018. Emerging fungal pathogen Candida auris evades neutrophil attack. MBio 9: e01403-18. doi: 10.1128/mBio.01403-18 30131360 PMC6106086 source
The OBSERVATION section reports that human neutrophils rarely engaged C. auris and proposes that it goes unrecognized by them. It does not establish that cell wall mannan masks immunostimulatory components or causes this evasion; the authors say the molecular mechanisms remain to be unraveled. No page numbers are provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans.
“However, neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans (21, 24).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [21] Johnson CJ, Davis JM, Huttenlocher A, Kernien JF, Nett JE. 2018. Emerging fungal pathogen Candida auris evades neutrophil attack. MBio 9: e01403-18. doi: 10.1128/mBio.01403-18 30131360 PMC6106086 source
- cites [24] Horton MV, Johnson CJ, Zarnowski R, Andes BD, Schoen TJ, Kernien JF, Lowman D, Kruppa MD, Ma Z, Williams DL, Huttenlocher A, Nett JE. 2021. Candida auris cell wall mannosylation contributes to neutrophil evasion through pathways divergent from Candida albicans and Candida glabrata. mSphere 6: e0040621. doi: 10.1128/mSphere.00406-21 34160238 PMC8265655 source
- Premisecitation
The biofilm matrix mannan-glucan complex is linked to the antifungal resistance biofilm phenotype via sequestration of antifungal.
“This complex has been linked to the antifungal resistance biofilm phenotype via sequestration of antifungal (20, 22).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [20] Mitchell KF, Zarnowski R, Sanchez H, Edward JA, Reinicke EL, Nett JE, Mitchell AP, Andes DR. 2015. Community participation in biofilm matrix assembly and function. Proc Natl Acad Sci U S A 112: 4092– 4097. doi: 10.1073/pnas.1421437112 25770218 PMC4386410 source
- cites [22] Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H, Cain MT, Hamaker J, Mitchell AP, Andes DR. 2012. A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog 8: e1002848. doi: 10.1371/journal.ppat.1002848 22876186 PMC3410897 source
The Results section, “Glucan modifying enzymes contribute to biofilm matrix-associated antifungal resistance” (page not available), links matrix glucan deposition to fluconazole sequestration and biofilm drug resistance. It does not identify a mannan–glucan complex as the material responsible, so that specific part of the claim is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Premisecitation
Cell wall mannan plays a role in neutrophil evasion by masking both glucan and chitin PAMPs.
“Cell wall mannan has also been shown to play a role in neutrophil evasion by masking both glucan and chitin PAMPs (21, 24).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [21] Johnson CJ, Davis JM, Huttenlocher A, Kernien JF, Nett JE. 2018. Emerging fungal pathogen Candida auris evades neutrophil attack. MBio 9: e01403-18. doi: 10.1128/mBio.01403-18 30131360 PMC6106086 source
The OBSERVATION section reports that C. auris evades human neutrophil engagement and killing. It does not show that cell-wall mannan causes this evasion or masks glucan and chitin PAMPs; searches for mannan, chitin, and cell-wall masking found no such finding in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [24] Horton MV, Johnson CJ, Zarnowski R, Andes BD, Schoen TJ, Kernien JF, Lowman D, Kruppa MD, Ma Z, Williams DL, Huttenlocher A, Nett JE. 2021. Candida auris cell wall mannosylation contributes to neutrophil evasion through pathways divergent from Candida albicans and Candida glabrata. mSphere 6: e0040621. doi: 10.1128/mSphere.00406-21 34160238 PMC8265655 source
- Findingown data
Exogenous wild-type EV addition to mnt5∆ biofilm returned toward the reference C. auris wild-type resistant phenotype.
“We observed a return of the mnt5∆ mutant susceptibility phenotype toward the wild-type C. auris-resistant phenotype.”
Quote in the paperSubstantial claim - Findingown data
MNT5 is important for C. auris biofilm drug resistance.
“Screen of mutants from a mannosyltransferase family identified the importance of MNT5 for C. auris biofilm drug resistance and neutrophil evasion.”
- Also stated in: § C. auris MNT5 impacts biofilm drug resistance · plain
“We found the biofilms of the mnt5∆ mutant to exhibit increased drug susceptibility during biofilm growth.”
Quote in the paperSubstantial claim - Also stated in: § C. auris MNT5 impacts biofilm drug resistance · plain
- Findingown data
The mnt5∆ mutant biofilms have a marked reduction in the community encasing extracellular matrix material.
“Imaging of the mnt5∆ mutant biofilms revealed a marked reduction in the community encasing extracellular matrix material (Fig. 1B).”
Quote in the paperSubstantial claim - Findingown data
MNT5 is important for C. auris neutrophil evasion.
“Screen of mutants from a mannosyltransferase family identified the importance of MNT5 for C. auris biofilm drug resistance and neutrophil evasion.”
- Also stated in: § Genetic disruption of C. auris mannosylation enhances neutrophil engagement · plain
“Neutrophils engaged the mnt5∆ mutant at a greater than threefold higher rate than the wild-type strain (Fig. 2A; Fig S2).”
Quote in the paperSubstantial claim - Also stated in: § Genetic disruption of C. auris mannosylation enhances neutrophil engagement · plain
- Findingown data
The mnt5∆ cell wall has a reduction in mannan.
“Analysis of the mnt5∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for MNT5 in mannan masking of pathogen-associated molecular patterns.”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ cell wall has a compensatory increase in cell surface glucan and chitin.
“Analysis of the mnt5∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for MNT5 in mannan masking of pathogen-associated molecular patterns.”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ mutant matrix and cell wall have alterations in mannan structures.
“Biochemical analysis of the mnt5∆ mutant matrix and cell wall identified alterations in the mannan structures.”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ mutant biofilm exhibits increased drug susceptibility during biofilm growth.
“We found the biofilms of the mnt5∆ mutant to exhibit increased drug susceptibility during biofilm growth.”
Quote in the paperSubstantial claim- Rests on an assumption: The mnt5∆ mutant does not have growth defects.
- Findingown data
Resistance and matrix for mnt5∆ were restored with delivery of wild-type matrix via extracellular vesicles.
“Resistance and matrix for mnt5∆ were restored with delivery of wild-type matrix via extracellular vesicles.”
Quote in the paperSubstantial claim - Findingown data
Antifungal treatment of the mnt5∆ biofilm resulted in more than double the fungal killing compared to wild-type.
“Compared to the wild-type, antifungal treatment of the mnt5∆ biofilm resulted in more than double the fungal killing (Fig. 1A).”
Quote in the paperSubstantial claim - Findingown data
The wild-type C. auris strain exhibited very little cell surface β-glucan or chitin.
“The wild-type C. auris strain exhibited very little cell surface β-glucan or chitin (Fig. 2F and G).”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ mutant cells are more prone to being engulfed by live neutrophils compared to wild-type.
“The mnt5∆ mutant cells are more prone to being engulfed by live neutrophils compared to the wild-type strain.”
Quote in the paperSubstantial claim - Findingown data
Neutrophils engaged the mnt5∆ mutant at a greater than threefold higher rate than the wild-type strain.
“Neutrophils engaged the mnt5∆ mutant at a greater than threefold higher rate than the wild-type strain (Fig. 2A; Fig S2).”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ mutant has a somewhat thicker cell wall compared to wild-type.
“Using transmission electron microscopy, we found a somewhat thicker cell wall for the mnt5∆ compared to wild-type stain (Fig. 2B and C).”
Quote in the paperNot a substantial claim - Findingown data
Other MNT mutants did not show changes in neutrophil engagement.
“We did not observe changes with the other MNT mutants.”
Quote in the paperSubstantial claim - Findingown data
The outer cell walls of the mnt5Δ mutant appeared less dense.
“In contrast, the outer cell walls of the mnt5Δ mutant appeared less dense.”
Quote in the paperSubstantial claim - Findingown data
A peak corresponding to β-Man in the β-Man-(1→2)-α-Man-(1→PO4 fragment was highly reduced in the mnt5∆ matrix.
“Spectral analysis of the mnt5∆ matrix revealed new peaks assigned to →2)-α-Man-(1→3) and →2)-β-Man-(1→, whereas a peak corresponding to β-Man in the β-Man-(1→2)-α-Man-(1→PO4 fragment was highly reduced in the mutant (Fig. 1D).”
Quote in the paperSubstantial claim - Findingown data
The mnt5∆ mutant displays increased amounts of β-glucan on the cell surface.
“C. auris mnt5∆ mutant displays increased amounts of β-glucan on the cell surface.”
Quote in the paperSubstantial claim - Findingown data
The glucan was higher in mnt5∆ (92.4%) compared to wild-type (79.5%).
“The proportion of mannan was lower in mutant (7.5%) compared to the wild-type (20.5%), while the glucan was higher in the mnt5∆ mutant (92.4%) compared to the wild-type (79.5%), consistent with a compensatory increase glucan (Fig. 2F).”
Quote in the paperSubstantial claim - Findingown data
Surface presentation of chitin is increased in the mnt5∆ mutant compared to wild-type.
“Surface presentation of chitin is increased in the C. auris mnt5∆ mutant compared to the wild-type strain.”
Quote in the paperSubstantial claim - Findingown data
The proportion of mannan residues was slightly increased in the mnt5∆ mutant (97.7%) compared to wild-type (92.6%).
“The proportion of mannan residues was slightly increased in the mnt5∆ mutant (97.7%) compared to the wild-type (92.6%), while the β-glucan content decreased in the mnt5∆ mutant (2.3%) compared to the wild-type (7.4%) (Fig. 1E and F).”
Quote in the paperNot a substantial claim - Findingown data
The mnt5∆ matrix has new peaks assigned to →2)-α-Man-(1→3) and →2)-β-Man-(1→.
“Spectral analysis of the mnt5∆ matrix revealed new peaks assigned to →2)-α-Man-(1→3) and →2)-β-Man-(1→, whereas a peak corresponding to β-Man in the β-Man-(1→2)-α-Man-(1→PO4 fragment was highly reduced in the mutant (Fig. 1D).”
Quote in the paperSubstantial claim - Findingown data
The proportion of mannan was lower in mnt5∆ (7.5%) compared to wild-type (20.5%).
“The proportion of mannan was lower in mutant (7.5%) compared to the wild-type (20.5%), while the glucan was higher in the mnt5∆ mutant (92.4%) compared to the wild-type (79.5%), consistent with a compensatory increase glucan (Fig. 2F).”
Quote in the paperSubstantial claim - Findingown data
The β-glucan content decreased in the mnt5∆ mutant (2.3%) compared to wild-type (7.4%).
“The proportion of mannan residues was slightly increased in the mnt5∆ mutant (97.7%) compared to the wild-type (92.6%), while the β-glucan content decreased in the mnt5∆ mutant (2.3%) compared to the wild-type (7.4%) (Fig. 1E and F).”
Quote in the paperSubstantial claim - Interpretationown data
MNT5 plays a role in mannan masking of pathogen-associated molecular patterns.
“Analysis of the mnt5∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for MNT5 in mannan masking of pathogen-associated molecular patterns.”
Quote in the paperSubstantial claim - Interpretationown data
MNT5 function in drug resistance is specific to the biofilm state.
“MNT5 disruption did not alter planktonic minimum inhibitory concentrations to fluconazole, suggesting that this MNT5 function is specific to the biofilm state (not shown).”
Quote in the paperSubstantial claim- Rests on an assumption: MNT5 disruption does not alter planktonic minimum inhibitory concentrations to fluconazole.
- Study design and conductown data
The increased drug susceptibility of mnt5∆ was reversed by genetic complementation, validating the mutants' genotype-phenotype relationship.
“The increased drug susceptibility was reversed by genetic complementation, thus validating the mutants’ genotype-phenotype relationship.”
Quote in the paperSubstantial claim - Interpretationown data
MNT5 participates in cell wall PAMP masking during immune recognition.
“In the present studies, we find that MNT5 also participates in cell wall PAMP masking during immune recognition.”
Quote in the paperSubstantial claim - Interpretationown data
The mnt5∆ cell wall has structural alterations in α-mannan with formation of unique moieties.
“Additionally, new signals (Unk6 and Unk7) emerged in the α-mannan region of the mnt5∆ mutant, all suggesting structural alterations in the α-mannan of the mnt5∆ cell wall with the formation of unique moieties (Fig. 2E; Table S6).”
Quote in the paperSubstantial claim - Study design and conductown data
Genetic complementation of mnt5∆ returned the host cell interaction toward the wild-type level of immune evasion.
“Genetic complementation of mnt5∆ mutant returned the host cell interaction toward the wild-type level of immune evasion.”
Quote in the paperSubstantial claim - Interpretationown data
The mnt5∆ mutant strains had increased electron-lucent layers, suggesting a compensatory increase in glucan and/or chitin.
“In addition, these mutant strains had increased electron-lucent layers, suggesting a compensatory increase in glucan and/or chitin.”
Quote in the paperNot a substantial claim - Interpretationown data
The loss of the outer layer in mnt5∆ is consistent with a decrease in cell wall mannan.
“This loss of the outer layer is consistent with a decrease in cell wall mannan.”
Quote in the paperSubstantial claim - Interpretationown data
MNT5 is important for delivery of functional biofilm matrix in an EV-dependent manner.
“This suggests that MTN5 is important for delivery of functional biofilm matrix in an EV-dependent manner (Fig. 1A and B).”
Quote in the paperSubstantial claim
- May combine two claims. 11
- Classified as probably not a substantial claim. 8
- The quote only partly states this claim. 2
May combine two claims.
InterpretationcitationC. auris MNT5 encodes a gene product that decreases cell wall α-mannosylation, resulting in a compensatory increase in cell wall glucan.
“Like its C. albicans, ortholog C. auris MNT5 also encodes a gene product that decreases cell wall α-mannosylation, perhaps by a decrease in α-1,2 mannan branches, resulting in a compensatory increase in cell wall glucan (16).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [16] Díaz-Jiménez DF, Mora-Montes HM, Hernández-Cervantes A, Luna-Arias JP, Gow NAR, Flores-Carreón A. 2012. Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis. Biochem Biophys Res Commun 419: 77– 82. doi: 10.1016/j.bbrc.2012.01.131 22326920 PMC3480643 source
The Introduction (page unavailable) says C. albicans Mnt5 adds mannose residues to cell-wall mannans, and the Discussion proposes that it adds mannose units to the N-mannan backbone. That is contrary to the sentence’s comparison with a C. albicans gene product that decreases mannosylation. The paper does not examine C. auris or report a compensatory increase in glucan. (LLM, conf=0.84)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationC. auris is an emerging fungal species responsible for healthcare-associated outbreaks and infections associated with relatively poor patient outcomes.
“Candida auris is an emerging fungal species responsible for healthcare-associated outbreaks and infections associated with relatively poor patient outcomes (1–6).”
Quote in the paperNot a substantial claim4 of 6 sources checked- cites [1] Adams E, Quinn M, Tsay S, Poirot E, Chaturvedi S, Southwick K, Greenko J, Fernandez R, Kallen A, Vallabhaneni S, Haley V, Hutton B, Blog D, Lutterloh E, Zucker H, Candida auris Investigation Workgroup. 2018. Candida auris in healthcare facilities, New York, USA, 2013-2017. Emerg Infect Dis 24: 1816– 1824. doi: 10.3201/eid2410.180649 30226155 PMC6154128 source
- cites [2] Bradley SF. 2019. Candida auris infection. JAMA 322: 1526. doi: 10.1001/jama.2019.13857 31613347 source
- cites [3] Casadevall A, Kontoyiannis DP, Robert V. 2019. On the emergence of Candida auris: climate change, azoles, swamps, and birds. MBio 10: e01397-19. doi: 10.1128/mBio.01397-19 31337723 PMC6650554 source
The Opinion/Hypothesis section describes C. auris as a newly emerged fungal pathogen associated with human disease and links clusters of cases to local infection-control issues. Our copy does not report patient outcomes or establish that those outcomes are relatively poor. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [4] Chowdhary A, Sharma C, Meis JF. 2017. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog 13: e1006290. doi: 10.1371/journal.ppat.1006290 28542486 PMC5436850 source
- cites [5] Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, Griffiths D, George S, Butcher L, Morgan M, Newnham R, Sunderland M, Clarke T, Foster D, Hoffman P, Borman AM, Johnson EM, Moore G, Brown CS, Walker AS, Peto TEA, Crook DW, Jeffery KJM. 2018. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med 379: 1322– 1331. doi: 10.1056/NEJMoa1714373 30281988 source
- cites [6] Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. 2017. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 64: 134– 140. doi: 10.1093/cid/ciw691 27988485 PMC5215215 source
May combine two claims.
PremisecitationClinical features of C. auris infections include biofilm persistence on abiotic surfaces and skin, immune evasion, and antifungal drug resistance.
“The clinical features of these infections include biofilm persistence on abiotic surfaces and skin, immune evasion, and antifungal drug resistance (7–12).”
Quote in the paperSubstantial claim5 of 6 sources checked- cites [7] Day AM, McNiff MM, da Silva Dantas A, Gow NAR, Quinn J. 2018. Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris. mSphere 3: e00506-18. doi: 10.1128/mSphere.00506-18 30355673 PMC6200985 source
The Introduction reports antifungal drug resistance, biofilm formation, persistent colonization of hospital wards and patients, and evasion of neutrophil-mediated killing. The Discussion notes detection on skin. Neither passage establishes that biofilms themselves persist on abiotic surfaces and skin, so that specific part of the claim is unsupported. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [8] Zamith-Miranda D, Heyman HM, Cleare LG, Couvillion SP, Clair GC, Bredeweg EL, Gacser A, Nimrichter L, Nakayasu ES, Nosanchuk JD. 2019. Multi-omics signature of Candida auris, an emerging and multidrug-resistant pathogen. mSystems 4: e00257-19. doi: 10.1128/mSystems.00257-19 31186339 PMC6561322 source
The Introduction reports C. auris on abiotic surfaces, biofilm production, resilience on hospital substrates, and antifungal resistance; the Results section on antifungal resistance documents a resistant clinical isolate. Our copy does not establish biofilm persistence on skin or immune evasion as features of C. auris infection. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [9] Kordalewska M, Lee A, Park S, Berrio I, Chowdhary A, Zhao Y, Perlin DS. 2018. Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob Agents Chemother 62: e00238-18. doi: 10.1128/AAC.00238-18 29632013 PMC5971591 source
- cites [10] Wall G, Herrera N, Lopez-Ribot JL. 2019. Repositionable compounds with antifungal activity against multidrug resistant Candida auris identified in the medicines for malaria venture's pathogen box. J Fungi (Basel) 5: 92. doi: 10.3390/jof5040092 31581540 PMC6958377 source
The Introduction reports that C. auris persists on surfaces and skin, frequently resists antifungal drugs, and forms biofilms that defend against immune cells. It does not establish that the biofilms themselves persist on skin; the skin-persistence statement concerns C. auris generally. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [11] Sherry L, Ramage G, Kean R, Borman A, Johnson EM, Richardson MD, Rautemaa-Richardson R. 2017. Biofilm-forming capability of highly virulent, multidrug-resistant Candida auris. Emerg Infect Dis 23: 328– 331. doi: 10.3201/eid2302.161320 28098553 PMC5324806 source
The Conclusions (page not provided) state that C. auris adheres to polymeric surfaces, forms biofilms, and resists antifungal agents, supporting the abiotic-surface and drug-resistance portions of the claim. The paper discusses disinfecting skin but does not establish biofilm persistence on skin or describe immune evasion. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [12] Horton MV, Johnson CJ, Kernien JF, Patel TD, Lam BC, Cheong JZA, Meudt JJ, Shanmuganayagam D, Kalan LR, Nett JE. 2020. Candida auris forms high-burden biofilms in skin niche conditions and on porcine skin. mSphere 5: e00910-19. doi: 10.1128/mSphere.00910-19 31969479 PMC6977180 source
The Introduction and Discussion (page unavailable) describe C. auris colonizing skin, persisting on hospital surfaces, and forming biofilms under skin-like conditions. The paper does not establish immune evasion or antifungal drug resistance as clinical features; searching those terms yielded references to other studies, not findings reported in the paper’s text. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn C. albicans, MNT5 is important for the addition of α-1,2 mannan branches.
“In C. albicans, MNT5 has been shown to be important for the addition of the α-1,2 mannan branches (16).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [16] Díaz-Jiménez DF, Mora-Montes HM, Hernández-Cervantes A, Luna-Arias JP, Gow NAR, Flores-Carreón A. 2012. Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis. Biochem Biophys Res Commun 419: 77– 82. doi: 10.1016/j.bbrc.2012.01.131 22326920 PMC3480643 source
The Discussion proposes that Mnt5 helps add the second mannose residue to lateral branches of the N-mannan outer chain. However, the Results state that the linkage of Mnt5’s enzymatic product could not be determined, so the paper does not establish the claimed α-1,2 linkage. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMuch of the matrix material is delivered via EVs and restoration of the matrix via exogenous administration of wild-type EVs returns the resistance biofilm properties.
“More recent investigations demonstrated that much of this matrix material is delivered via EVs and that restoration of the matrix via exogenous administration of wild-type EVs returns the resistance biofilm properties (28).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [28] Zarnowski Robert, Sanchez H, Covelli AS, Dominguez E, Jaromin A, Bernhardt J, Mitchell KF, Heiss C, Azadi P, Mitchell A, Andes DR. 2018. Candida albicans biofilm-induced vesicles confer drug resistance through matrix biogenesis. PLoS Biol 16: e2006872. doi: 10.1371/journal.pbio.2006872 30296253 PMC6209495 source
The EV add-back assay (Fig. 4) shows that wild-type EVs restored matrix production and fluconazole resistance in susceptible C. albicans mutant biofilms. The section “Production of distinctive biofilm EVs” suggests that EVs may supply a major share of matrix material, but treats the amount delivered as an inference, not a demonstrated fact; it also proposes a catalytic role for EV cargo. The claim overstates that part of the finding. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral Candida species produce a unique biofilm extracellular matrix mannan-glucan complex that is delivered via EVs.
“Several Candida species produce a unique biofilm extracellular matrix mannan-glucan complex that is delivered via EVs (25–28).”
Quote in the paperNot a substantial claim4 of 4 sources checked- cites [25] Zarnowski R, Sanchez H, Jaromin A, Zarnowska UJ, Nett JE, Mitchell AP, Andes D. 2022. A common vesicle proteome drives fungal biofilm development. Proc Natl Acad Sci U S A 119: e2211424119. doi: 10.1073/pnas.2211424119 36095193 PMC9501958 source
The Results (Comparison of Vesicle Cargo Composition; page unavailable) report that several Candida species produce biofilm vesicles containing mannan and glucan in ratios compatible with assembly of the matrix mannan–glucan complex. The paper says this suggests EV delivery of the complex’s building blocks; it does not establish that the assembled complex itself is delivered via EVs. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [26] Zarnowski R, Massey J, Mitchell AP, Andes D. 2022. Extracellular vesicles contribute to mixed-fungal species competition during biofilm initiation. MBio 13: e0298822. doi: 10.1128/mbio.02988-22 36377868 PMC9765065 source
The Observation section (page not specified) says that several Candida species secrete core polysaccharides in extracellular vesicles and links vesicle cargo to biofilm matrix production. It does not identify that cargo as a unique mannan-glucan complex or establish that such a complex is delivered via EVs. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [27] Zarnowski Robert, Noll A, Chevrette MG, Sanchez H, Jones R, Anhalt H, Fossen J, Jaromin A, Currie C, Nett JE, Mitchell A, Andes DR. 2021. Coordination of fungal biofilm development by extracellular vesicle cargo. Nat Commun 12: 6235. doi: 10.1038/s41467-021-26525-z 34716343 PMC8556236 source
The Results section (‘ESCRT pathway directs vesicle cargo composition’; page unavailable) says C. albicans biofilm EVs deliver an adhesive extracellular matrix. The cited paper does not establish that several Candida species deliver a specifically mannan-glucan complex via EVs; its experiments focus on C. albicans. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [28] Zarnowski Robert, Sanchez H, Covelli AS, Dominguez E, Jaromin A, Bernhardt J, Mitchell KF, Heiss C, Azadi P, Mitchell A, Andes DR. 2018. Candida albicans biofilm-induced vesicles confer drug resistance through matrix biogenesis. PLoS Biol 16: e2006872. doi: 10.1371/journal.pbio.2006872 30296253 PMC6209495 source
The Introduction identifies a mannan–glucan complex in the C. albicans biofilm matrix and says EVs promote its assembly. The ‘Production of distinctive biofilm EVs’ section finds mannan and glucan in EV cargo but says vesicles may deliver material that forms the matrix, rather than establishing delivery of the intact complex. The paper does not establish this mechanism for several Candida species. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The quote only partly states this claim.
Findingown dataAddition of EVs from the mnt5∆ strain did not alter the mnt5∆ susceptible phenotype.
“Conversely, the addition of EVs from the mnt5∆ did not restore these reference biofilm phenotypes.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe extracellular matrix of wild-type and mnt5∆ mutant contained similar monosugar composition but differences in abundance of α-mannan, β-mannan, β-(1→6)-glucan, and β-(1→3)-glucan linkages.
“Nuclear magnetic resonance (NMR) analysis demonstrated that the extracellular matrix of the wild-type and mnt5∆ mutant contained similar monosugar composition but exhibited differences in the abundance of α- mannan, β-mannan, β-(1→6)-glucan, and β-(1→3)-glucan linkages (Fig. 1C; Table S7).”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataComparison of 2D 1H-1H COSY spectra revealed variations between C. auris wild-type and mnt5∆ mutant cell walls, including absence of Unk2 and Unk3, increased intensity of Unk1 and Unk4, and emergence of new Unk6 and Unk7 peaks in the α-mannan region.
“Comparison of 2D 1H-1H COSY spectra revealed variations between C. auris wild-type and mnt5∆ mutant cell walls. The Unk2 and Unk3 signals were absent in the mnt5∆ mutant (shown in red squares), while the Unk1 and Unk4 peaks became more intense. The 2D COSY spectra confirmed differences in peak shapes in the α-mannan region, with lower intensity peaks in the mnt5∆ mutant compared to the wild-type.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe mnt5∆ cell wall has a general decrease in mannan content and a relative compensatory increase in β1,3- and β1,6-glucan components compared to wild-type.
“For the mnt5∆ cell wall, we observed a general decrease in the mannan content and a relative compensatory increase in the β1,3- and β1,6-glucan components, when compared to wild-type.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe wild-type strain exhibits a dense, well-defined mannan-rich outer layer and a more lucent inner cell wall layer containing glucan and chitin.
“The wild-type strain exhibited a dense, well-defined mannan-rich outer layer. Adjacent to this, we observed a more lucent inner cell wall layer, which has been shown to contain glucan and chitin residues.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe mnt5Δ strain displayed both β-glucan and chitin, with over 12- and 6-fold greater PAMP exposure compared to wild-type.
“In contrast, the mnt5Δ strain displayed both β-glucan and chitin, with quantification of fluorescence revealing over 12- and 6-fold greater PAMP exposure compared to the wild-type strain, respectively.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn C. albicans, several mannan production and modification genes modulate matrix accumulation, and their disruption eliminates the protective antifungal shield, rendering the biofilm communities drug susceptible.
“In C. albicans, several mannan production and modification genes modulate matrix accumulation, and their disruption eliminates the protective antifungal shield, rendering the biofilm communities drug susceptible (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Mitchell KF, Zarnowski R, Sanchez H, Edward JA, Reinicke EL, Nett JE, Mitchell AP, Andes DR. 2015. Community participation in biofilm matrix assembly and function. Proc Natl Acad Sci U S A 112: 4092– 4097. doi: 10.1073/pnas.1421437112 25770218 PMC4386410 source
Classified as probably not a substantial claim.
PremisecitationCell wall and biofilm matrix mannan play roles in Candida biology including cell adherence, biofilm formation, and host response.
“Cell wall and biofilm matrix mannan play roles in numerous components of Candida biology including cell adherence, biofilm formation, and host response (20).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Mitchell KF, Zarnowski R, Sanchez H, Edward JA, Reinicke EL, Nett JE, Mitchell AP, Andes DR. 2015. Community participation in biofilm matrix assembly and function. Proc Natl Acad Sci U S A 112: 4092– 4097. doi: 10.1073/pnas.1421437112 25770218 PMC4386410 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationC. auris cell walls contain a higher abundance of N-linked mannans compared to O-linked mannans.
“The cell walls of C. auris, like C. albicans, contain a higher abundance of N-linked mannans compared to O-linked mannans (23).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Gow NAR, Lenardon MD. 2023. Architecture of the dynamic fungal cell wall. Nat Rev Microbiol 21: 248– 259. doi: 10.1038/s41579-022-00796-9 36266346 source
May combine two claims.
Interpretationown dataThe mnt5∆ matrix has altered α-mannan structures and new moieties.
“This finding is consistent with altered α-mannan structures and new moieties in the biofilm extracellular matrix of mnt5∆ mutant.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNeutrophils are essential for the host response to Candida.
“Neutrophils are essential for the host response to Candida (29, 30).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [29] Mansour MK, Levitz SM. 2002. Interactions of fungi with phagocytes. Curr Opin Microbiol 5: 359– 365. doi: 10.1016/s1369-5274(02)00342-9 12160853 source
- cites [30] Lehrer RI, Cline MJ. 1969. Interaction of Candida albicans with human leukocytes and serum. J Bacteriol 98: 996– 1004. doi: 10.1128/jb.98.3.996-1004.1969 4182532 PMC315286 source
The paper relies on this without support.
Many mechanisms underlying C. auris biofilm persistence, immune evasion, and antifungal drug resistance remain largely unknown.
“Many of the mechanisms underlying these distinct phenotypes remain largely unknown.”
The paper relies on this without support.
MNT5 disruption does not alter planktonic minimum inhibitory concentrations to fluconazole.
“MNT5 disruption did not alter planktonic minimum inhibitory concentrations to fluconazole, suggesting that this MNT5 function is specific to the biofilm state (not shown).”
The paper relies on this without support.
The mnt5∆ mutant does not have growth defects.
“Growth defects were not noted (not shown).”
The paper relies on this without support.
MNT5 does not impact fungal growth or fitness in a mouse infection model.
“While the MNT5 does not impact fungal growth or fitness in a mouse infection model (not shown)”
The paper relies on this without support.
Genetic regulation of mannosylation pathways in C. auris is largely unexplored compared to C. albicans.
“Compared to C. albicans, genetic regulation of mannosylation pathways has been largely unexplored for C. auris.”
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.
Cell-surface chitin is cited to the wrong figure panel
MinorThe text cites Fig. 2F and G for cell-surface β-glucan and chitin, respectively, but the figure caption identifies chitin as panel H; panel F reports cell-wall glucan and mannan proportions.
“The wild-type C. auris strain exhibited very little cell surface β-glucan or chitin (Fig. 2F and G).”
“(H) Surface presentation of chitin is increased in the C. auris mnt5∆ mutant compared to the wild-type strain.”
MNT5's stated effect on cell-wall mannosylation is reversed
MinorThe discussion says the MNT5 gene product decreases cell-wall α-mannosylation, but the reported mutant results show decreased mannan after MNT5 disruption. The stated direction of MNT5's effect conflicts with the paper's findings.
“Like its C. albicans, ortholog C. auris MNT5 also encodes a gene product that decreases cell wall α-mannosylation, perhaps by a decrease in α-1,2 mannan branches, resulting in a compensatory increase in cell wall glucan (16).”
“For the mnt5∆ cell wall, we observed a general decrease in the mannan content and a relative compensatory increase in the β1,3- and β1,6-glucan components, when compared to wild-type.”
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Self-citationA Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance
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Self-citation<i>Candida auris</i> in Healthcare Facilities, New York, USA, 2013–2017
Adams, E., Quinn, M., Tsay, S., Poirot, E., Chaturvedi, S., Southwick, K., Greenko, J., Fernandez, R., Kallen, A., Vallabhaneni, S., et al. (2018) · Emerging Infectious Diseases · doi:10.3201/eid2410.180649 · Cited by 284 · see citing works
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Self-citationUnderstanding Echinocandin Resistance in the Emerging Pathogen Candida auris
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“Cell wall and biofilm matrix mannan play roles in numerous components of Candida biology including cell adherence, biofilm formation, and host response (20).”
Self-citationCandida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin
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Self-citationEmerging fungal pathogen Candida auris evades neutrophil attack
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“However, neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans (21, 24).”
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“Cell wall and biofilm matrix mannan play roles in numerous components of Candida biology including cell adherence, biofilm formation, and host response (20).”
InfluentialConserved Role for Biofilm Matrix Polysaccharides in <i>Candida auris</i> Drug Resistance
Dominguez, E. G., Zarnowski, R., Choy, H. L., Zhao, M., Sanchez, H., Nett, J. E., & Andes, D. R. (2019) · mSphere · doi:10.1128/mspheredirect.00680-18 · Cited by 132 · cited 1× · see citing works
“Previous studies have demonstrated the importance of the extracellular matrix in protection of the Candida biofilm community from antifungal drugs, including for C. auris (17, 18, 22).”
Self-citationHall, R. A., Bates, S., Lenardon, M. D., MacCallum, D. M., Wagener, J., Lowman, D. W., Kruppa, M. D., Williams, D. L., Odds, F. C., Brown, A. J. P., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003276 · Cited by 128 · see citing works
Coordination of fungal biofilm development by extracellular vesicle cargo
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Self-citationHog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris
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“%) compared to the wild-type (79.5%), while the mannan content was lower in the mnt5 ∆ mutant (7.5”
InfluentialMulti-omics Signature of <i>Candida auris</i> , an Emerging and Multidrug-Resistant Pathogen
Zamith-Miranda, D., Heyman, H. M., Cleare, L. G., Couvillion, S. P., Clair, G. C., Bredeweg, E. L., Gacser, A., Nimrichter, L., Nakayasu, E. S., & Nosanchuk, J. D. (2019) · mSystems · doi:10.1128/msystems.00257-19 · Cited by 99 · see citing works
<i>Candida auris</i> : multi-omics signature of an emerging and multidrug-resistant pathogen
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“However, neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans (21, 24).”
Self-citationDominguez, E., Zarnowski, R., Sanchez, H., Covelli, A. S., Westler, W. M., Azadi, P., Nett, J., Mitchell, A. P., & Andes, D. R. (2018) · mBio · doi:10.1128/mbio.00451-18 · Cited by 77 · cited 1× · see citing works
“Previous studies have demonstrated the importance of the extracellular matrix in protection of the Candida biofilm community from antifungal drugs, including for C. auris (17, 18, 22).”
Self-citationA common vesicle proteome drives fungal biofilm development
Zarnowski, R., Sanchez, H., Jaromin, A., Zarnowska, U. J., Nett, J. E., Mitchell, A. P., & Andes, D. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211424119 · Cited by 63 · see citing works
Self-citationWall, G., Herrera, N., & Lopez-Ribot, J. L. (2019) · Journal of Fungi · doi:10.3390/jof5040092 · Cited by 58 · see citing works
Díaz-Jiménez, D. F., Mora-Montes, H. M., Hernández-Cervantes, A., Luna-Arias, J. P., Gow, N. A. R., & Flores-Carreón, A. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.01.131 · Cited by 54 · cited 2× · see citing works
“Like its C. albicans , ortholog C. auris MNT5 also encodes a gene product that decreases cell wall α-mannosylation, perhaps by a decrease in α-1,2 mannan branches, resulting in a compensatory increase in cell wall glucan (16).”
Extracellular vesicles contribute to mixed-fungal species competition during biofilm initiation
Zarnowski, R., Massey, J., Mitchell, A. P., & Andes, D. (2022) · mBio · doi:10.1128/mbio.02988-22 · Cited by 15 · see citing works
Self-citation<i>Candida auris</i> Infection
Bradley, S. F. (2019) · JAMA · doi:10.1001/jama.2019.13857 · Cited by 13 · see citing works
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Candida auris : host interactions, antifungal drug resistance, and diagnostics
Chowdhary, A., Lionakis, M. S., & Chauhan, N. (2025) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00187-22 · Cited by 14 · see citing works
“The importance of C. auris mannans in antifungal drug resistance and host interactions has recently been demonstrated by the role of several mannosylation genes, such as PMR1 , VAN1 , and MNT5, in biofilm drug resistance and neutrophil engagement (64, 65).”
Liu, L. L., Niu, T., Zhang, T., Tan, D., Duan, X., & Li, X. (2026) · Microbiological Research · doi:10.1016/j.micres.2026.128542
Insights on molecular drivers of phenotypic plasticity in Candidozyma auris
Solanki, S., Singh, B., Mathur, K., Asif, S., Francis, A., Gangwar, G., Thakur, A. S., & Puria, R. (2026) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-026-05085-8
“For example MNT5 deletion in C. auris showed increased neutrophil engagement due to less dense outer mannan layer leading to compensatory increase in chitin and glucan (Zarnowski et al. 2025).”
Holt, A. M., Horton, M. V., Johnson, C. J., Żarnowski, R., Vang, P. C., Dean, M., Kaas, A., Andes, B. D., Jones, R., Lowman, D. W., et al. (2026) · mBio · doi:10.1128/mbio.01701-26
Self-citationSoni, A., Vrzoňová, R., Paulovičová, L., Bzducha‐Wróbel, A., & Farkaš, P. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.154672
- Authors
- Zarnowski, R., Horton, M. V., Johnson, C. J., Vang, P. C., Uram, J., Fernando, L. D. P., Vlach, J., Heiss, C., Azadi, P., Nett, J. E., & Andes, D. R.
- Affiliations
- Department of Medicine, University of Wisconsin-Madison
- University of Wisconsin–Madison (US)
- University of Georgia (US)
- ORCID
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2025-04-09
- Volume
- 16
- Issue
- 4
- Pages
- e0034625-e0034625
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC11980391
- OpenAlex
- W4407913617
- Cited by
- 5
- References
- 30
- Citations by year
- 2026: 4 · 2025: 1
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (R01 AI073289-16, R01 AI145939)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida auris, mannosyltransferase, biofilm, antifungal resistance, mannan, extracellular vesicles, cell wall composition, glucan, chitin, pathogen-associated molecular patterns, immune evasion, therapeutic target
- MeSH terms
- Candida auris, Antifungal Agents, Cell Wall, Chitin, Fungal Proteins, Glucans, Humans, Mannans, Mannosyltransferases, Neutrophils, Biofilms, Drug Resistance, Fungal, Immune Evasion
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-20.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-20.
Cited sources are checked by gpt-6-sol.
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 ›
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