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Cited by 0Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris

Open access
Liang, Weihong, Guan, Shuyun, Bing, Jian, Du, Han, Zheng, Qiushi, Tao, Li, Li, Bing, Huang, Guanghua +1 more·2026·npj Biofilms and Microbiomes
DOI 10.1038/s41522-026-01043-2PMC PMC13586155
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Abstract

The emerging fungal pathogen Candida auris is a serious global public health threat due to its ability to persist in healthcare environments and on human skin. Here, we report a prevalent cluster of clinical C. auris strains with enhanced biofilm formation, a contributor to environmental and skin persistence. Genomic analyses show that the clinical isolates with enhanced biofilm formation ability carry a loss-of-function mutation in the WOR2 locus, which encodes a white-opaque switching regulator in Candida species. Analysis of 13,314 published genomes revealed that 3104 strains (23.3%) harbor nonsense or frameshift mutations in WOR2, indicating frequent clinical occurrence. Deletion of WOR2 in a clinical strain markedly increased biofilm formation, whereas reintroduction of an intact WOR2 significantly attenuated biofilm development. Further analyses show that Wor2 inactivation upregulates GFC1, ALS4, and multiple biofilm-associated genes. Together, these findings reveal a key regulatory mechanism underlying biofilm development, environmental persistence, and transmission of C. auris.

AI snapshot

Written from the paper’s full text.

TL;DR

Loss-of-function mutations in the *WOR2* phenotypic switching regulator are common in clinical *Candida auris* and enhance biofilm formation. Wor2 acts as a negative regulator of biofilm development, likely through Gfc1- and Als4-dependent pathways.

Key findings

  • Among 82 clinical *C. auris* isolates from China, a subset showed enhanced biofilm formation; whole-genome sequencing found 6/11 (54.5%) high-biofilm isolates carried missense, nonsense, or frameshift mutations in *WOR2*.
  • Analysis of 13,314 published genomes found 3,104 strains (23.3%) with nonsense or frameshift *WOR2* mutations: 29.7% (1,846/6,217) of Clade I, 0.9% (48/5,426) of Clade III, and 73.7% (1,210/1,641) of Clade IV; no *WOR2* mutations were found in Clade II.
  • Reintroducing intact *WOR2* into clinical mutant strains reduced biofilm formation, while *WOR2* deletion in strain GZ10 increased biofilm formation and *WOR2* overexpression attenuated it.
  • Transcriptomic analysis identified 606 differentially expressed genes between four *wor2* mutants and strain GZ10: 145 upregulated and 461 downregulated; adhesion/biofilm genes including *ALS4*, *BRG1*, *NDT80*, *ECM33*, and *GFC1* were upregulated in mutants.

Methods

  • The study used 82 clinical *C. auris* isolates from China, whole-genome sequencing, phylogenetic and pairwise SNP analyses, and genomic screening of 13,314 publicly available *C. auris* genomes from NCBI.
  • Biofilm formation was quantified by CFU assays in 48-well polystyrene plates and visualized by SEM on silicone squares; mutant strains were constructed by homologous recombination, complementation, and overexpression.
  • Skin colonization used newborn female BALB/c mice (3–4 days old, 2–3 g) inoculated with 1 × 10^7 cells; transcriptomic profiling used RNA-seq with three biological replicates, RT-PCR normalized to *ACT1*, and WGCNA for co-expression analysis.

Limitations

  • The paper states that publicly available genome sequences are heavily biased toward the United States (96.3% of *wor2* mutant strains, 2,989/3,104), so the overall 23.3% mutation frequency may not reflect the real global frequency due to sampling bias and regional outbreak dynamics.
  • The paper states that the detailed regulatory mechanism remains incomplete and future work is needed to identify direct binding targets of Wor2 and Gfc1 and to determine why *WOR2* mutations are clade-dependent.
  • The paper notes that the newborn mouse skin immune microenvironment differs from that of humans, although the model allows stable *C. auris* colonization without skin injury.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41522-026-01043-2

Cites

56 of 59 references verified0 citation errors · 3 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

26 of 37 cited sources checked · 14 supported · 1 flagged · accuracy not yet measured

  • Interpretationreasoning

    The WOR2 mutation could contribute to the prevalence and rapid transmission of C. auris.

    “Since biofilms are often associated with increased persistence on the environmental surfaces and colonization on host skin4,5,11,49, this mutation could contribute to the prevalence and rapid transmission of C. auris.”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [4] Du, H. et al. Candida auris: epidemiology, biology, antifungal resistance, and virulence. PLoS Path 16, e1008921 (2020). source
    • cites [5] Santana, D. J., Zhao, G. & O’Meara, T. R. The many faces of Candida auris: phenotypic and strain variation in an emerging pathogen. PLoS Path 20, e1012011 (2024). source
    • cites [11] Horton, M. V. & Nett, J. E. Candida auris infection and biofilm formation: going beyond the surface. Curr. Clin. Microbiol. Rep. 7, 51–56 (2020). source
    • cites [49] Ramage, G., Kean, R., Rautemaa-Richardson, R., Williams, C. & Lopez-Ribot, J. L. Fungal biofilms in human health and disease. Nat. Rev. Microbiol. 23, 355–370 (2025). source
  • Findingown data

    Among sequenced Candida auris strains with enhanced biofilm-forming ability (CFU > 5 × 10^7 cells per well, 11 isolates), 6 strains (54.5%) harbored a missense, nonsense, or frameshift mutation in WOR2.

    “Among the sequenced strains with enhanced biofilm-forming ability (CFU > 5 × 107 cells per well, 11 isolates), 6 strains (6/11, 54.5%) harbored a missense, non-sense, or frameshift mutation in the WOR2 locus”
    Quote in the paperSubstantial claim
  • Findingown data

    Clinical Candida auris isolates with enhanced biofilm formation carry a loss-of-function mutation in the WOR2 locus.

    “Genomic analyses show that the clinical isolates with enhanced biofilm formation ability carry a loss-of-function mutation in the WOR2 locus, which encodes a white–opaque switching regulator in Candida species.”
    Quote in the paperSubstantial claim
  • Findingown data

    Pairwise SNP differences among eight WOR2 mutant Candida auris strains ranged from 2 to 31 SNPs.

    “with pairwise SNP differences among the eight WOR2 mutant strains ranging from merely 2 to 31 SNPs”
    Quote in the paperNot a substantial claim
  • Findingown data

    Phylogenetic analysis indicated a very close relationship between GZ109, GZ82, GZ126 and contemporaneous clinical isolate GZ55, which contained an intact WOR2 gene.

    “Phylogenetic analysis indicated a very close relationship between these three mutant strains and a contemporaneous clinical isolate GZ55, which contained an intact WOR2 gene”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 22
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    The cell wall adhesin Als4 plays a central role in biofilm formation in C. auris and is required for adhesion to both biotic and abiotic surfaces.

    “The cell wall adhesin Als4 plays a central role in biofilm formation in C. auris and is required for adhesion to both biotic and abiotic surfaces11,14,17,50,52.”
    Quote in the paperSubstantial claim5 of 5 sources checked
    • cites [11] Horton, M. V. & Nett, J. E. Candida auris infection and biofilm formation: going beyond the surface. Curr. Clin. Microbiol. Rep. 7, 51–56 (2020). source

      The sections on biofilms in healthcare settings describe C. auris growing as adherent biofilms on skin and catheter surfaces. They do not identify Als4 or establish that it is central to biofilm formation or required for adhesion to either surface type (searched: Als4 and adhesin-mediated adhesion). (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [14] Santana, D. J. et al. A Candida auris–specific adhesin, scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source

      In “Polymer surface attachment by the adhesin SCF1” (page not provided), the paper reports that, among twelve ALS- and IFF/HYR-family deletion mutants tested, only loss of IFF4109 impaired adhesion to the tested polymer surface. Its summary identifies SCF1—not Als4—as critical for biofilm formation and colonization of biological and abiotic surfaces. The copy therefore contradicts the claim that Als4 is required for adhesion to both kinds of surface. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [17] Zhao, G. et al. Adhesin als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins. Nat. Commun. 16, 5673 (2025). source

      The Introduction (page unavailable) reports that variation in ALS4 copy number is linked to variation in biofilm formation and surface colonization. It does not establish that Als4 is required for adhesion to both biotic and abiotic surfaces. The paper’s own adhesion experiments instead focus on Als4112 and its interactions with keratinocytes and extracellular matrix proteins. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [50] Nobile, C. J. et al. Complementary adhesin function in C. albicans biofilm formation. Curr. Biol. 18, 1017–1024 (2008). source

      The Results section (“Functional relationships among Als1, Als3, and other Als proteins”; page unavailable) reports that Als4 overexpression restored biofilm formation in vitro in C. albicans, but did not rescue biofilm formation in its in vivo catheter model. The paper does not establish a central or required role for Als4 in C. auris, or show that it is required for adhesion to both biotic and abiotic surfaces. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [52] Horton, M. V., Holt, A. M. & Nett, J. E. Mechanisms of pathogenicity for the emerging fungus Candida auris. PLoS Path 19, e1011843 (2023). source

      The “Adhesion, biofilm formation, and environmental persistence” section (page not provided) says ALS4 expression correlates with aggregation and heightened biofilm formation across C. auris isolates. It does not establish that Als4 is required for adhesion to either biotic or abiotic surfaces, and “central role” is stronger than the reported correlation. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    WOR2 encodes a transcription factor required for white-opaque phenotypic switching in Candida albicans.

    “It has been demonstrated that WOR2 encodes a transcription factor required for white-opaque phenotypic switching in C. albicans32,33.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [32] Hernday, A. D. et al. Structure of the transcriptional network controlling white-opaque switching in Candida albicans. Mol. Microbiol. 90, 22–35 (2013). source
    • cites [33] Zordan, R. E., Miller, M. G., Galgoczy, D. J., Tuch, B. B. & Johnson, A. D. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 5, e256 (2007). source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Biofilm formation enhances Candida auris adhesive capacity and colonization efficiency.

    “with biofilm formation enhancing its adhesive capacity and colonization efficiency9–11”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [9] Bing, J. et al. Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of als4. PLoS Path 19, e1011239 (2023). source

      The Results section on skin colonization (page unavailable) reports that the strain with robust biofilms also showed the strongest colonization of newborn mouse skin. The Discussion (page unavailable) attributes enhanced adherence and biofilm formation to ALS4 amplification; it does not show that biofilm formation itself increases adhesive capacity or causes more efficient colonization. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [10] Horton, M. V. et al. Candida auris forms high-burden biofilms in skin niche conditions and on porcine skin. MSphere 5, 00910-00919 https://doi.org/10.1128/msphere (2020). source
    • cites [11] Horton, M. V. & Nett, J. E. Candida auris infection and biofilm formation: going beyond the surface. Curr. Clin. Microbiol. Rep. 7, 51–56 (2020). source

      The section ‘Does C. auris form biofilms in healthcare settings?’ describes biofilms as adherent communities and says growth as a biofilm on skin likely contributes to C. auris colonization. It does not establish that forming a biofilm increases the organism’s adhesive capacity relative to non-biofilm growth. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida auris can persistently colonize human skin.

    “C. auris exhibits a particular tropism for the skin6–8. It is capable of persistent colonization in niches such as the axillae and groin”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [6] Proctor, D. M. et al. Clonal Candida auris and eskape pathogens on the skin of residents of nursing homes. Nature 639, 1016–1023 (2025). source
    • cites [7] Rossow, J. et al. Factors associated with Candida auris colonization and transmission in skilled nursing facilities with ventilator units, New York, 2016–2018. Clin. Infect. Dis. 72, e753–e760 (2021). source
    • cites [8] Proctor, D. M. et al. Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility. Nat. Med. 27, 1401–1409 (2021). source

  • Classified as probably not a substantial claim.

    Premisecitation

    The Bcr1 transcription factor is required for the expression of several cell wall adhesins in C. albicans.

    “As a key regulator of biofilm development, the Bcr1 transcription factor is required for the expression of several cell wall adhesins in C. albicans28,29,50,51.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [28] Nobile, C. J., Nett, J. E., Andes, D. R. & Mitchell, A. P. Function of Candida albicans adhesin hwp1 in biofilm formation. Eukaryot. Cell 5, 1604–1610 (2006). source
    • cites [29] Nobile, C. J. & Mitchell, A. P. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor bcr1p. Curr. Biol. 15, 1150–1155 (2005). source
    • cites [50] Nobile, C. J. et al. Complementary adhesin function in C. albicans biofilm formation. Curr. Biol. 18, 1017–1024 (2008). source
    • cites [51] Fanning, S. et al. Divergent targets of Candida albicans biofilm regulator bcr1 in vitro and in vivo. Eukaryot. Cell 11, 896–904 (2012). source

  • Classified as probably not a substantial claim.

    Premisecitation

    Gfc1, the homolog of Candida albicans Bcr1, plays a critical regulatory role in hyphal formation and biofilm development in pathogenic Candida species.

    “It has been known that the Gfc1 (the homolog of C. albicans Bcr1) transcription factor plays a critical regulatory role in hyphal formation and biofilm development in pathogenic Candida species29,47,48.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [29] Nobile, C. J. & Mitchell, A. P. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor bcr1p. Curr. Biol. 15, 1150–1155 (2005). source
    • cites [47] Guan, G. et al. Bcr 1 plays a central role in the regulation of opaque cell filamentation in Candida albicans. Mol. Microbiol. 89, 732–750 (2013). source

      The Discussion (page not available) describes Bcr1 as a regulator of biofilm development and reports this study’s finding that it regulates opaque-cell filamentation in C. albicans. The copy does not identify Gfc1 as a Bcr1 homolog or establish that Gfc1 regulates hyphal formation and biofilm development across pathogenic Candida species; a search for Gfc1 found no matching passage. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [48] Deng, Y. et al. A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris. PLoS Path 20, e1012362 (2024). source

      The Discussion identifies C. albicans Bcr1 as Gfc1’s closest homolog, and the Results show that Gfc1 negatively regulates filamentous growth in C. auris. The Discussion attributes biofilm development to Bcr1 in C. albicans white cells, not to Gfc1, and does not establish Gfc1’s role across pathogenic Candida species. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    BRG1, NDT80, and GFC1 encode three transcription factors that are core regulators of biofilm development in Candida albicans.

    “BRG1, NDT80, and GFC1 encode three transcription factors that are core regulators of biofilm development in C. albicans27,34.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [27] Nobile, C. J. et al. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148, 126–138 (2012). source

      The Results section identifies BRG1 and NDT80 as transcription regulators required for normal C. albicans biofilm formation. It names six core biofilm regulators, but not GFC1; a search for GFC1 found no matching passage in our copy. Page numbers were not provided. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [34] Timpel, C., Strahl-Bolsinger, S., Ziegelbauer, K. & Ernst, J. F. Multiple functions of pmt1p-mediated proteino-mannosylation in the fungal pathogen Candida albicans. J. Biol. Chem. 273, 20837–20846 (1998). source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ALS4 is a member of the Als family, which plays a critical role in the regulation of biofilm formation in Candida auris.

    “ALS4 is a member of the Als family, which plays a critical role in the regulation of biofilm formation in C. auris9,13,17,18.”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [9] Bing, J. et al. Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of als4. PLoS Path 19, e1011239 (2023). source
    • cites [13] Kean, R. et al. Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. Msphere 3, 00334-00318 https://doi.org/10.1128/msphere (2018). source
    • cites [17] Zhao, G. et al. Adhesin als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins. Nat. Commun. 16, 5673 (2025). source
    • cites [18] Wang, T. W. et al. Functional redundancy in Candida auris cell surface adhesins crucial for cell-cell interaction and aggregation. Nat. Commun. 15, 9212 (2024). source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Biofilms are often associated with increased persistence on environmental surfaces and colonization on host skin.

    “Since biofilms are often associated with increased persistence on the environmental surfaces and colonization on host skin4,5,11,49, this mutation could contribute to the prevalence and rapid transmission of C. auris.”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [4] Du, H. et al. Candida auris: epidemiology, biology, antifungal resistance, and virulence. PLoS Path 16, e1008921 (2020). source

      The Biology section’s “Biofilm development” subsection says C. auris biofilms contribute to survival in the environment and likely in the host, supporting the environmental-persistence part of the claim. The paper discusses skin colonization separately in relation to filamentous cells, but does not specifically associate biofilms with increased colonization of host skin. Page numbers are unavailable in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [5] Santana, D. J., Zhao, G. & O’Meara, T. R. The many faces of Candida auris: phenotypic and strain variation in an emerging pathogen. PLoS Path 20, e1012011 (2024). source
    • cites [11] Horton, M. V. & Nett, J. E. Candida auris infection and biofilm formation: going beyond the surface. Curr. Clin. Microbiol. Rep. 7, 51–56 (2020). source
    • cites [49] Ramage, G., Kean, R., Rautemaa-Richardson, R., Williams, C. & Lopez-Ribot, J. L. Fungal biofilms in human health and disease. Nat. Rev. Microbiol. 23, 355–370 (2025). source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In C. albicans, Wor2 is required for white-to-opaque switching and maintenance of the opaque cell type under regular culture conditions.

    “In C. albicans, Wor2 is required for white-to-opaque switching and maintenance of the opaque cell type under regular culture conditions32,33.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [32] Hernday, A. D. et al. Structure of the transcriptional network controlling white-opaque switching in Candida albicans. Mol. Microbiol. 90, 22–35 (2013). source

      The Introduction states that Wor2 is required for heritable maintenance of the opaque cell type, supporting that part of the claim. The Results identify Wor2 as part of the switching circuit and indicate that deleting core regulators affects switching rates, but the copy does not establish that Wor2 is required for the white-to-opaque transition under regular culture conditions. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [33] Zordan, R. E., Miller, M. G., Galgoczy, D. J., Tuch, B. B. & Johnson, A. D. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 5, e256 (2007). source

  • May combine two claims.

    Findingown data

    Wor2 inactivation upregulates GFC1, ALS4, and multiple biofilm-associated genes.

    “Further analyses show that Wor2 inactivation upregulates GFC1, ALS4, and multiple biofilm-associated genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Strains GZ109, GZ82, and GZ126 carried an identical WOR2 nonsense mutation (p.Q180*) and were isolated from the same patient at 20-30 day intervals.

    “Of note, strains GZ109, GZ82 and GZ126, which carried an identical WOR2 nonsense mutation (p.Q180*), were isolated from the same patient at 20–30 day intervals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared to strain GZ10, a subset of genes associated with adhesion and biofilm development including ALS4, BRG1, NDT80, ECM33, and GFC1 were upregulated in wor2 mutants, whereas several cell wall-related genes including YWP1, CHS1 and PGA26 were downregulated.

    “compared to the reference strain GZ10, a subset of genes associated with adhesion and biofilm development including ALS4, BRG1, NDT80, ECM33, and GFC1, were upregulated in the wor2 mutants, whereas several cell wall-related genes including YWP1, CHS1 and PGA26 were downregulated”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In both silicone square and 48-well plate assays, GZ126, WOR2-reconstituted and both genes-reconstituted strains exhibited remarkably attenuated biofilm formation, whereas the GFC1-reconstituted strain developed robust biofilms.

    “In both silicone square and 48-well plate assays, strain GZ126, the WOR2-reconstituted and both genes-reconstituted strains exhibited remarkably attenuated biofilm formation (Fig. 7b, d, f), whereas the GFC1-reconstituted strain developed robust biofilms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The two later Candida auris isolates GZ82 and GZ109 had only a WOR2 mutation and lacked the GFC1 frameshift mutation.

    “The two later isolates, GZ82 and GZ109 with only WOR2 mutation and lacking the GFC1 frameshift mutation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The wor2Δgfc1Δ double mutant and WOR2-reconstituted strains exhibited severely defective biofilm development, while the GFC1-reconstituted strain (wor2Δgfc1Δ + GFC1) formed robust biofilms.

    “the wor2Δgfc1Δ double mutant and WOR2-reconstituted strains exhibited a severely defective biofilm development, while the GFC1-reconstituted strain (wor2Δgfc1Δ + GFC1) formed robust biofilms”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Loss-of-function mutations in WOR2 are prevalent among clinical C. auris isolates, reaching 23.3% overall and exceeding 70% in Clade IV strains.

    “In the present study, we report that loss-of-function mutation of WOR2, which encodes a transcription factor required for phenotypic switching in pathogenic Candida species, is prevalent in clinical strains of C. auris and leads to an enhanced biofilm-forming capacity.”
    • Also stated in: § Discussion · boosted
      “The prevalence of loss-of-function mutations in WOR2 among clinical isolates is strikingly high, reaching 23.3% overall and exceeding 70% in Clade IV strains (Figs. 2 and S4 Table)”
    • Also stated in: § Discussion · boosted
      “In the current study, we demonstrate that loss of function mutations of WOR2 occurred at high frequency (23.3%) among clinical strains”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of the differentially expressed genes, 145 genes were upregulated and 461 genes were downregulated in the wor2 mutants.

    “Of the DEGs, 145 genes were upregulated and 461 genes were downregulated in the wor2 mutants”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Three Candida auris isolates (GZ126, GZ82, GZ109) were obtained from the same patient over a 30-day period.

    “Notably, three isolates (GZ126, GZ82, GZ109) obtained from the same patient over a 30-days period.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The WOR2 mutant cluster has recent common ancestry and clonal expansion.

    “strongly supporting their recent common ancestry and clonal expansion”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida auris poses a serious and growing threat to global public health.

    “Candida auris poses a serious and growing threat to global public health1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Organization, W. H. Who fungal priority pathogens list to guide research, development and public health action (World Health Organization, 2022).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    Inactivating mutations in WOR2 lead to increased expression of the adhesin gene ALS4, and this process is affected by GFC1.

    “Inactivating mutations in WOR2 lead to increased expression of the adhesin gene ALS4 and this process is affected by GFC1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Spontaneous mutation of WOR2 in clinical isolates could benefit C. auris as a pathogen.

    “Given the importance of biofilm formation in pathogenesis, spontaneous mutation of this gene in clinical isolates could benefit C. auris as a pathogen, which perhaps represents an environmental adaptation strategy.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Biofilm formation is important in pathogenesis.

  • May combine two claims.

    Interpretationown data

    Gfc1 has a potential promoting effect on biofilm formation and skin colonization.

    “suggesting that Gfc1 has a potential promoting effect on biofilm formation and skin colonization”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Deletion of WOR2 leads to enhanced biofilm development, while overexpression of this gene suppresses biofilm development in Candida auris.

    “These results indicate that deletion of WOR2 leads to enhanced biofilm development, while overexpression of this gene suppresses biofilm development.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    To control for litter effects, each independent animal experiment included pups from at least 2-3 different dams.

    “To control for litter effects, each independent experiment included pups from at least 2–3 different dams.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    This mechanism likely represents a key evolutionary strategy adopted by C. auris to thrive in the healthcare setting.

    “This mechanism likely represents a key evolutionary strategy adopted by C. auris to thrive in the healthcare setting.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    All experiments were performed with at least three independent replicates.

    “To ensure reproducibility, all experiments were performed with at least three independent replicates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Gene expression levels were normalized to the C. auris ACT1 gene.

    “Gene expression levels were normalized to the C. auris ACT1 gene.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Overexpression of WOR2 was validated by PCR and RT-PCR.

    “The overexpression was validated by PCR and RT-PCR.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All C. auris isolates were identified by sequencing the 28S D1/D2 region of rDNA and the 18S internal transcribed spacer (ITS), and their identity was further confirmed by genomic sequencing.

    “All C. auris isolates were identified by sequencing the 28S D1/D2 region of rDNA and the 18S internal transcribed spacer (ITS), and their identity was further confirmed by genomic sequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductnone given

    For RT-PCR, each biological replicate comprised three independent samples and included three technical replicates.

    “For RT-PCR analysis, each biological replicate comprised three independent samples.”
    • Also stated in: § RNA-seq and RT-PCR · plain
      “Each biological replicate included three technical replicates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Complementation of WOR2 and GFC1 was validated by PCR and Sanger sequencing.

    “The complementation was validated by PCR and Sanger sequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Pups from the same litter were randomly distributed across all experimental groups (mutant, reconstituted, WT) to avoid confounding by litter-specific factors.

    “Pups from the same litter were randomly distributed across all experimental groups (mutant, reconstituted, WT) to avoid confounding by litter-specific factors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Each strain was analyzed with three biological replicate samples for RNA-seq.

    “Each strain was analyzed with three biological replicate samples.”
    Quote in the paperNot a substantial claim
35 of 35

  • The authors state this as an assumption.

    Candida auris does not undergo white–opaque switching.

    “Given that C. auris does not undergo white–opaque switching”

  • The paper relies on this without support.

    Our understanding of the upstream signaling pathways that regulate adhesins during biofilm formation remains limited.

    “Despite recent advances, our understanding of the upstream signaling pathways that regulate adhesins during biofilm formation remains limited.”

  • The paper relies on this without support.

    White–opaque switching is absent in C. auris.

    “Consistent with the absence of white–opaque switching in C. auris, our findings indicate that Wor2 could have been evolutionarily repurposed to function as a negative regulator of biofilm formation.”

  • The paper relies on this without support.

    Biofilm formation is important in pathogenesis.

    “Given the importance of biofilm formation in pathogenesis, spontaneous mutation of this gene in clinical isolates could benefit C. auris as a pathogen, which perhaps represents an environmental adaptation strategy.”

  • The paper relies on this without support.

    There are few detailed mechanistic analyses linking specific genomic mutations in clinical isolates to virulence phenotypes.

    “Despite the surging case numbers of C. auris globally, there are still few detailed mechanistic analyses linking specific genomic mutations in clinical isolates to virulence phenotypes.”
5 of 5

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.

  • Conflicting SEM fixatives

    Minor

    The Fig. 3 caption says the silicone-square biofilms were fixed with glutaraldehyde, while the SEM methods say samples were fixed with pentanediol. These are different fixatives, leaving the preparation of the SEM samples inconsistent.

1 of 1

Cites

Flagged first, then by citations

3 of the 62 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Kean, R. et al. Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. Msphere 3, 00334-00318 https://doi.org/10.1128/msphere (2018). · DOI
  2. Day, A. M., McNiff, M. M., da Silva Dantas, A., Gow, N. A. & Quinn, J. Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris. MSphere 3, 00506-00518 https://doi.org/10.1128/msphere (2018). · DOI
  3. Shivarathri, R. et al. The two-component response regulator ssk1 and the mitogen-activated protein kinase hog1 control antifungal drug resistance and cell wall architecture of Candida auris. MSphere 5, 00973–00920 https://doi.org/10.1128/msphere (2020). · DOI

Authors
Liang, W., Guan, S., Bing, J., Du, H., Zheng, Q., Tao, L., Li, B., Huang, G., & Chu, H.
Affiliations
  • Tongji University (CN)
  • Fudan University (CN)
  • Southwest University (CN)
Corresponding author
  • Li, Bing
  • Huang, Guanghua
  • Chu, Haiqing
ORCID
Venue
npj Biofilms and Microbiomes
Publisher
Springer Science and Business Media LLC
Published
2026-06-08
Volume
12
Issue
1
ISSN
2055-5008 (ISSN-L)
DOI
10.1038/s41522-026-01043-2
PMC
PMC13586155
OpenAlex
W7163881814
Cited by
0
References
62
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Biofilms and Microbiomes (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Shanghai Pujiang Program (24PJD124)
  • National Natural Science Foundation of China (32170193, 32370202, 32530005)
  • National Key Research and Development Program of China (2025YFE0205500)
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, white-opaque switching, phenotypic switching, biofilm formation, loss-of-function mutations, environmental persistence, clinical isolates, gene deletion and complementation
MeSH terms
Loss of Function Mutation, Candida auris, Candidiasis, Fungal Proteins, Humans, Phenotype, Gene Expression Regulation, Fungal, Biofilms

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.

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