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Cited by 33Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins

Open access
Zhao, Guolei, Lyu, Jingwen, Veniaminova, Natalia A., Zarnowski, Robert, Mattos, Eliciane, Johnson, Chad J., Quintanilla, Derek, Hautau, Haley +17 more·2025·Nature Communications
DOI 10.1038/s41467-025-60876-1PMC PMC12214902
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Abstract

Candida auris is a fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. Here, we show that a C. auris conserved adhesin, Als4112, is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix proteins, especially basement membrane proteins such as laminin. Deletion of ALS4112 reduces skin colonization in mouse models of epicutaneous and systemic infection. In addition, coating plastic and catheter surfaces with collagen I or III inhibits C. auris attachment and biofilm formation. Our study highlights the critical role of Als4112 in C. auris colonization and virulence, and explores potential strategies to reduce the pathogen’s adherence to abiotic surfaces and thus its spread in healthcare settings. Candida auris is a fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. Here, Zhao et al. explore the mechanisms driving pathogen’s adherence to skin, involving a conserved adhesin, as well as the potential of collagen coatings as a strategy to reduce C. auris adherence to abiotic surfaces.

AI snapshot

Written from the paper’s full text.

TL;DR

The Candida auris adhesin Als4112 is the major mediator of keratinocyte adherence across clades and also binds specific skin extracellular matrix proteins, especially laminin. Deleting ALS4112 reduces skin colonization and systemic virulence in mice, while collagen I/III coatings inhibit C. auris attachment and biofilm formation on plastic and catheters.

Key findings

  • ALS4112 deletion caused minimal keratinocyte adherence across representative Clades I–IV, with complementation restoring wild-type adherence; overexpression in low-adherent AR0382 raised adhesion to Chicago4-like levels, and anti-NDV-3A serum reduced Chicago4 keratinocyte adherence by ~30%.
  • Across 33 C. auris isolates from five clades, ALS4112 transcript abundance positively correlated with keratinocyte adhesion (r = 0.7441, P < 0.0001).
  • In murine epicutaneous colonization, wild-type Chicago4 reached an average log10 CFU of ~6.3, whereas Δals4112 showed an average 7-fold decrease; complementation restored burden. In systemic infection, Δals4112 gave 60% survival and median survival >21 days versus wild-type 100% mortality and median survival 11.5 days (P = 0.0008).
  • C. auris bound tropoelastin, collagen V, and laminin but not collagen I, III, IV, VI, fibronectin, or vitronectin; Δals4112 showed 50% reduced adherence to laminin. Collagen I or III coating inhibited plastic/catheter attachment and biofilm, with an average 6-fold decrease on collagen III-coated rat central venous catheters.

Methods

  • In vitro assays used human N/TERT keratinocytes and ECM protein arrays; a forward genetic screen tested 1,595 Agrobacterium-mediated insertional mutants in Chicago4 for keratinocyte adhesion defects, followed by deletion/complement strain construction and validation across clades.
  • In vivo work included murine epicutaneous skin colonization in C57BL/6 mice (n = 5), systemic infection in immunosuppressed CD-1 mice (n = 10 per group for survival), and rat central venous catheter colonization (n = 3 rats).
  • Analyses included one-way ANOVA with Dunnett’s test, two-sided unpaired t tests, Pearson correlation, and Mantel-Cox log-rank survival analysis; fungal burden was measured by CFU normalized to tissue weight and delivered inoculum.

Limitations

  • The paper states that isolated keratinocytes cannot fully capture differentiated keratinocyte layers or the complete array of skin ECM proteins, and that the mutagenesis screen was not saturating, so additional genes likely remain to be found.
  • The paper reports that the ALS4112 complement strain had subtelomeric shortening and loss of adjacent genes including IFF4109 and IFF4110, which may explain incomplete virulence complementation; ex vivo human skin colonization was preliminary, based on two biological replicates.
  • Evident from the text: most mechanistic and in vivo conclusions rely on specific strain backgrounds and mouse/rat models, and strain-specific differences in adhesin use were observed, so generalization across all C. auris isolates is not fully established.

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

Integrity signals

Registry

Crossref · 10.1038/s41467-025-60876-1

Cites

84 of 84 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

38 of 67 cited sources checked · 18 supported · 0 flagged · accuracy not yet measured

  • Interpretationreasoning

    C. auris has an enhanced ability to colonize high-sweat body sites such as the axillae or inguinal crease.

    “This suggests an enhanced ability of C. auris to colonize high-sweat body sites, such as the axillae or inguinal crease, which is corroborated by clinical sampling10,19.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [10] 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

      The Results section, “Patterns of body-site colonization with C. auris” (page unavailable), documents colonization of the axilla and inguinal crease. It does not establish an enhanced ability to colonize high-sweat sites: the nares had significantly higher fungal burdens than either site, and the paper does not assess sweat as an explanation. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [19] Proctor, D. M. et al. Clonal Candida auris and ESKAPE pathogens on the skin of residents of nursing homes. Nature https://doi.org/10.1038/s41586-025-08608-9 (2025). source
  • Findingown data

    Keratinocyte adherence varies between representative C. auris strains from four clades.

    “we tested the adherence capacity of representative C. auris isolates from four clades (Fig. 1a). Consistent with previous reports on plastic adhesion29 and skin adherence21, we observed variation in keratinocyte adherence between these four representative strains (Fig. 1a).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [29] Santana, D. J. et al. A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source

      In “C. auris relies on SCF1 for adhesive plasticity” (Fig. 2B; page not available), the paper reports substantial adhesion variation among 23 isolates from all five clades. But that comparison concerns adhesion to polymer surfaces, not keratinocytes; the copy does not establish variation in keratinocyte adherence among the four strains described in the citing sentence. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source

      The Results section (“Candida auris Persistently Colonizes Skin”; page unavailable) reports that four C. auris clades colonized wild-type mouse skin at different levels. It does not report variation in adherence to keratinocytes, the specific outcome attributed to it here. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.
  • Premisecitation

    IFF4109 has previously been implicated in C. auris systemic infection.

    “Notably, IFF4109 has previously been implicated in C. auris systemic infection29.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Santana, D. J. et al. A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source
  • Findingown data

    There is strain-specific variation in human keratinocyte adherence among C. auris clinical isolates.

    “We observed strain-specific variation in human keratinocyte adherence among C. auris clinical isolates, which aligns with previous findings of the varied skin colonization abilities in a murine model21.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source
  • Premisecitation

    The Hog1 MAP kinase is essential for skin colonization in a murine model.

    “The Hog1 MAP kinase is essential for skin colonization in a murine model36.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [36] Shivarathri, R. et al. The Candida auris Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence. MBio 15, e0274824 (2024). source
  • Classified as probably not a substantial claim. 35
  • May combine two claims. 40
  • The quote only partly states this claim. 1

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

    Premisecitation

    C. auris adhesins Scf1 and Iff4109 promote skin colonization and disease.

    “Our recent study demonstrated the role of two adhesins, Scf1 and Iff4109, in promoting skin colonization and disease29.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Santana, D. J. et al. A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source

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

    Premisecitation

    C. albicans Als3 adhesin binds to epithelial cell receptors E-cadherin, EGFR, Her2, and c-Met, and to macrophage receptor CR3.

    “the Als3 adhesin of C. albicans binds to receptors on epithelial cells, such as E-cadherin, EGFR, Her2, and c-Met, and receptors on macrophages, such as CR325–28.”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [25] Phan, Q. T. et al. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 5, e64 (2007). source

      The section “Als3 Is Necessary for C. albicans to Bind to N-Cadherin on Endothelial Cells and E-Cadherin on Oral Epithelial Cells” supports Als3-dependent binding to epithelial E-cadherin. The passages found do not establish binding to EGFR, Her2, c-Met, or macrophage CR3. Page numbers were not provided in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [26] Zhu, W. et al. EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection. Proc. Natl Acad. Sci. Usa. 109, 14194–14199 (2012). source
    • cites [27] Phan, Q. T. et al. Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection. PLoS Pathog. 19, e1011579 (2023). source

      The Introduction says c-Met interacts with Als3, and the Results (Fig. 6 model) place Als3 in an oral epithelial-cell complex containing E-cadherin, EGFR, HER2, and c-Met. That supports the epithelial-receptor association, but does not establish that Als3 binds each receptor directly. The paper does not address Als3 binding to macrophage CR3 (searched: CR3, macrophage receptor). (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [28] Zhou, T. et al. Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans. Nat. Commun. 15, 3926 (2024). source

      The Discussion (page not available in our copy) says Als3 adheres to endothelial or epithelial cells via E-cadherin, EGFR, and HER2. The Results section on hyphal Als proteins and CR3 (page not available) reports direct binding between purified Als3 and CR3 and examines that interaction in macrophages. The cited paper does not identify c-Met as an Als3 receptor; searches for c-Met and the MET receptor found no supporting passage. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a murine skin colonization model, C. auris isolates from different clades show strain-specific differences in colonization capacity, with one Clade III isolate exhibiting the highest fungal burden 14 days post-inoculation.

    “an in vivo murine skin colonization model sampling C. auris isolates from different clades demonstrated strain-specific differences in colonization capacity, with one Clade III isolate exhibiting the highest fungal burden 14 days post-inoculation21.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source

      The Results section (‘Candida auris Persistently Colonizes Skin’; page unavailable) reports that four clades colonized mouse skin at different levels and that the African clade had the highest topical colonization two weeks after exposure. Our copy does not identify the African clade as Clade III, so it does not establish that specific designation. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    C. auris can reside deep in the skin, particularly within hair follicles, and persists in tissue for up to four months even when surface swabs are negative.

    “Histopathology revealed that C. auris can reside deep into the skin, particularly within hair follicles. The fungus persisted in the tissue for up to four months, even when surface swabs yielded negative cultures”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source

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

    Premisecitation

    Anti-Als3 antibodies generated by the NDV-3A vaccine target ALS adhesin proteins on the C. auris surface, disrupting adhesion, biofilm formation, and opsonophagocytic killing.

    “Anti-Als3 protein antibodies, generated in response to the vaccine containing the N-terminal region of C. albicans Als3 protein, specifically target ALS adhesin proteins on the C. auris surface, resulting in disruption of adhesion, biofilm formation, and opsonophagocytic killing30.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [30] Singh, S. et al. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection. PLoS Pathog. 15, e1007460 (2019). source

      The Results sections on antibody binding and biofilms show that NDV-3A-induced anti-Als3p antibodies bind C. auris surface homologs and that vaccinated-mouse sera inhibit biofilm formation. The paper does not separately demonstrate disrupted adhesion, and its Results say the antibodies enhance—not disrupt—opsonophagocytic killing. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    C. auris can establish high-level colonization on the skin and persist for months.

    “A key factor contributing to the high transmissibility of C. auris is its ability to readily establish high level colonization on the skin and persistently present for months5,10,16,17.”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [5] Pacilli, M. et al. Regional emergence of Candida auris in Chicago and lessons learned from intensive follow-up at 1 ventilator-capable skilled nursing facility. Clin. Infect. Dis. 71, e718–e725 (2020). source

      The Results (vSNF-A Chicago Facility Case Study; page not specified) document colonization across repeated surveys from January to October 2018, and the Discussion describes persistent colonization over long periods. The Methods identify axillary/groin skin swabs as the surveillance samples. The paper does not establish that skin colonization is readily acquired or consistently high-level. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [10] 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

      The Results (Longitudinal analysis of C. auris colonization; page unavailable) report skin sites dominated by C. auris and persistent colonization, with a model forecasting persistence for over a year. But the same section says commensal skin communities resist initial invasion and rarely transition directly to C. auris predominance, so the citing sentence’s claim that high-level colonization is established ‘readily’ overstates the evidence. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [16] Vallabhaneni, S. et al. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus-United States, may 2013-august 2016. Am. J. Transpl. 17, 296–299 (2017). source
    • cites [17] Schelenz, S. et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob. Resist. Infect. Control 5, 35 (2016). source

      The Discussion reports rapid colonization of patients’ skin, high transmissibility, and continued colonization despite daily chlorhexidine washes. The Results also describe a heavily colonized patient. Neither passage establishes that skin colonization persists for months in an individual patient; the 16-month period describes the outbreak, not the duration of colonization. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    In C. albicans, targeting adhesin proteins with vaccines decreases adhesion to and biofilm formation on plastic surfaces, invasion of vaginal epithelial cells, and virulence.

    “In the model fungal pathogen C. albicans, targeting adhesin proteins with vaccines results in a decrease in adhesion to and biofilm formation on plastic surfaces, including catheters, invasion of vaginal epithelial cells, and virulence22–24.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [22] Uppuluri, P. et al. Human anti-Als3p antibodies are surrogate markers of NDV-3A vaccine efficacy against recurrent vulvovaginal candidiasis. Front. Immunol. 9, 1349 (2018). source

      The Results (‘Sera From NR Patients Reduced C. albicans Biofilm Development’ and ‘…Invasion of Vaginal Epithelial Cells’; pages unavailable) report reduced adhesion, biofilm formation on plastic and catheter material, and vaginal epithelial-cell invasion with sera from vaccinated patients whose candidiasis did not recur. The Introduction also reports reduced disease severity in vaccinated mice. The claim omits the restriction to particular patients’ sera for the in vitro findings and presents the effects as a general result of adhesin-targeting vaccines. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [23] Alqarihi, A., Singh, S., Edwards, J. E. Jr, Ibrahim, A. S. & Uppuluri, P. NDV-3A vaccination prevents C. albicans colonization of jugular vein catheters in mice. Sci. Rep. 9, 6194 (2019). source
    • cites [24] Edwards, J. E. et al. A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis—A phase 2 randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 66, 1928–1936 (2018). source

      The paper describes NDV-3A as targeting Als3, an adhesin/invasin and virulence factor, and reports fewer symptomatic vaginal candidiasis recurrences after vaccination in women under 40 (Introduction and Results; page numbers unavailable). It does not report that vaccination decreased adhesion or biofilm formation on plastic or catheters, invasion of vaginal epithelial cells, or fungal virulence directly. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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

    Premisecitation

    C. auris persistently colonizes patient skin and adheres to abiotic surfaces, creating reservoirs that enable prolonged transmission in healthcare settings.

    “These outbreaks are marked by the pathogen’s ability to persistently colonize patient skin and adhere to abiotic surfaces, creating reservoirs that enable prolonged transmission within healthcare settings9–15.”
    Quote in the paperSubstantial claim3 of 7 sources checked
    • cites [9] Sexton, D. J. et al. Positive correlation between Candida auris skin-colonization burden and environmental contamination at a ventilator-capable skilled nursing facility in Chicago. Clin. Infect. Dis. 73, 1142–1148 (2021). source
    • cites [10] 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

      The Results (Longitudinal analysis of C. auris colonization) report persistent skin colonization, and the Abstract says shedding into the healthcare environment creates a reservoir for ongoing transmission. Our copy does not establish the distinct claim that C. auris adheres to abiotic surfaces; a reference to another study of survival on plastic does not demonstrate adherence here. Page numbers are unavailable in the indexed passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [11] Adams, E. et al. Candida auris in healthcare facilities, New York, USA, 2013-2017. Emerg. Infect. Dis. 24, 1816–1824 (2018). source
    • cites [12] Dire, O., Ahmad, A., Duze, S. & Patel, M. Survival of Candida auris on environmental surface materials and low-level resistance to disinfectant. J. Hosp. Infect. 137, 17–23 (2023). source
    • cites [13] Nobrega de Almeida, J. et al. Axillary Digital Thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil. Mycoses 64, 1062–1072 (2021). source
    • cites [14] Eyre, D. W. et al. A Candida auris outbreak and its control in an intensive care setting. N. Engl. J. Med. 379, 1322–1331 (2018). source
    • cites [15] Patterson, C. A. et al. Cloth lanyards as a source of intermittent transmission of Candida auris on an ICU. Crit. Care Med. 49, 697–701 (2021). source

  • May combine two claims.

    Premisecitation

    In an in vitro artificial human axillary sweat medium, C. auris achieves a fungal burden 10 times greater than C. albicans and persists during colonization for over 14 days, whereas C. albicans does not.

    “In an in vitro model using an artificial human axillary sweat medium, C. auris achieves a fungal burden 10 times greater than Candida albicans and persists during colonization for over 14 days, which was not observed in C. albicans18.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Horton, M. V. et al. Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin. mSphere 5, e00910–e00919 (2020). source

      The Results section (“C. auris forms high-burden biofilms in skin milieu”) reports a 10-fold greater C. auris biofilm burden than C. albicans in synthetic sweat medium. The Results section on desiccation reports viable C. auris at 14 days postdesiccation, while C. albicans biofilms were not viable. It does not establish persistence for over 14 days or describe that result as persistence during colonization. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Whole-genome sequencing and insertion mapping identified an insertion in B9J08_004112, encoding the ALS adhesin Als4112, and in B9J08_003899, encoding a Mub1 homolog.

    “We used whole-genome sequencing and insertion mapping to identify an insertion in the gene B9J08_004112, which encodes an ALS adhesin protein on the cell surface, referred to as Als411229, and in the gene B9J08_003899, which encodes a protein homologous to the Saccharomyces cerevisiae Mub1 protein, a subunit of a ubiquitin ligase complex44.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [29] Santana, D. J. et al. A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source
    • cites [44] Ju, D., Wang, X., Xu, H. & Xie, Y. Genome-wide analysis identifies MYND-domain protein Mub1 as an essential factor for Rpn4 ubiquitylation. Mol. Cell. Biol. 28, 1404–1412 (2008). source

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

    Premisecitation

    NDV-3A vaccination significantly improves protection of mice against hematogenous disseminated C. auris infections.

    “NDV-3A vaccination significantly improves the protection of mice against hematogenous disseminated C. auris infections30.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [30] Singh, S. et al. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection. PLoS Pathog. 15, e1007460 (2019). source

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

    Premisecitation

    Copy number variation of ALS4 accounts for variation in biofilm formation, surface colonization, and virulence among C. auris isolates, and Als4 amplification is linked to improved skin colonization during natural evolution.

    “Bing and colleagues showed that copy number variation of ALS4 accounts for variation in biofilm formation, surface colonization, and virulence among isolates, linking Als4 amplification to improved skin colonization during natural evolution31.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Bing, J. et al. Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4. PLoS Pathog. 19, e1011239 (2023). source

      The Results sections on ALS4 copy-number variation and skin colonization link amplified ALS4 to enhanced biofilm formation and show that strain SJ02 colonized newborn mouse skin more robustly than the comparison strains. The virulence Results report decreased, not increased, virulence for SJ02 in a Galleria infection model. The paper documents copy-number changes in clinical isolates, but does not show that ALS4 amplification improved skin colonization during natural evolution. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Previous reports show C. auris residing on the skin surface and within hair follicles.

    “This observation aligns with previous reports of C. auris residing on the skin surface and within hair follicles21,45.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source
    • cites [45] Merrill, E. D. et al. The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles. bioRxivorg https://doi.org/10.1101/2025.01.15.632653 (2025). source

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

    Premisecitation

    Previous findings in a murine model showed varied skin colonization abilities.

    “which aligns with previous findings of the varied skin colonization abilities in a murine model21.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Huang, X. et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29, 210–221.e6 (2021). source

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

    Premisecitation

    Previously, the authors reported that C. auris adhesins Scf1 and Iff4109 contribute to skin colonization.

    “Previously, we reported that two C. auris adhesins, Scf1 and Iff4109, contribute to skin colonization29”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Santana, D. J. et al. A Candida auris–specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381, 1461–1467 (2023). source

  • May combine two claims.

    Premisecitation

    C. auris can readily colonize human skin, and shedding from patient skin is considered one of the reservoirs for nosocomial contamination by C. auris.

    “The highly transmissible fungal pathogen C. auris can readily colonize human skin and shedding from patient skin is considered one of the reservoirs for nosocomial contamination by C. auris10,16.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [10] 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
    • cites [16] Vallabhaneni, S. et al. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus-United States, may 2013-august 2016. Am. J. Transpl. 17, 296–299 (2017). source

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

    Premisecitation

    Previous studies show that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions.

    “This agrees with previous studies showing that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions52,53.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [52] Raposo, C. J., McElroy, K. A. & Fuchs, S. M. The Epithelial adhesin 1 tandem repeat region mediates protein display through multiple mechanisms. FEMS Yeast Res. 20, foaa018 (2020). source

      The Abstract reports that Epa1p tandem-repeat copy number affects surface display, shedding, and protein function; the Results section on shedding reports less shedding as copy number increases. Our copy does not link repeat copy number to cell-surface hydrophobicity. Its Introduction mentions a hydrophobic signal peptide, which is a different property. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [53] Frank, A. T. et al. Structure and function of glycosylated tandem repeats from Candida albicans Als adhesins. Eukaryot. Cell 9, 405–414 (2010). source

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

    Premisecitation

    A previous report showed a correlation between genomic amplification of ALS4 and enhanced skin colonization in C. auris clinical isolates.

    “This is consistent with a previous report showing a correlation between genomic amplification of ALS4 and enhanced skin colonization in C. auris clinical isolates31.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Bing, J. et al. Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4. PLoS Pathog. 19, e1011239 (2023). source

  • Classified as probably not a substantial claim.

    Premisecitation

    No sex bias has been observed in the rat external jugular venous catheter biofilm model.

    “Experiments were conducted using male rats as no sex bias has been observed in this model, thus reducing the extraneous use of animals82,83.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [82] Andes, D. et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect. Immun. 72, 6023–6031 (2004). source
    • cites [83] Nett, J. E., Marchillo, K. & Andes, D. R. Modeling of fungal biofilms using a rat central vein catheter. Methods Mol. Biol. 845, 547–556 (2012). source

      The Introduction describes the rat jugular-vein catheter biofilm model, and Methods §3.4 describes animal care, but neither reports a comparison between male and female rats or addresses sex bias. Searches for sex bias, sex differences, and male rats found no passage supporting that claim. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The complement strain exhibits partial restoration of virulence and a higher number of lesions compared to the Δals4112 mutant.

    “The complement strain exhibited a partial restoration of virulence and a higher number of lesions compared to the Δals4112 mutant”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The murine systemic infection model reflects human C. auris systemic infection.

  • May combine two claims.

    Findingown data

    The reduction in C. auris adhesion on collagen I- or III-coated plastic is observed across all four clades, although the extent of reduction varies among clades.

    “Remarkably, this reduction in adhesion was observed across all four clades of C. auris, underscoring the broad efficacy of specific collagen coatings in preventing colonization, although the extent of reduction varied among clades (Fig. 7b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Whole-genome sequencing revealed subtelomeric shortening in the complemented strain, accompanied by loss of adjacent genes including B9J08_004111 and two adhesin-encoding genes, IFF4109 and IFF4110.

    “whole-genome sequencing revealed subtelomeric shortening in the complemented strain, accompanied by the loss of adjacent genes, including B9J08_004111 and two adhesin-encoding genes, IFF4109 and IFF4110 (Fig. S2C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    By two days post-infection, C. auris forms a dense coating on the skin surface, coats hair shafts, and resides in hair follicles.

    “By two days post-infection, C. auris had formed a dense coating on the skin surface, robustly coating the hair shafts and residing in the hair follicle (Fig. 5a).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The murine epicutaneous skin colonization model reflects human C. auris skin colonization.

  • May combine two claims.

    Findingown data

    Adhering C. auris cells remain on the surface of keratinocytes and are not internalized even at four hours of coincubation.

    “we differentially stained internal and external fungal cells and observed that the adhering C. auris cells remained on the surface of keratinocytes even at four hours of coincubation (Fig. 1c).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.

  • The quote only partly states this claim.

    Findingown data

    A similar pattern of reduced colonization in Δals4112 was observed in preliminary ex vivo human skin colonization assays based on two biological replicates.

    “A similar pattern was observed in preliminary ex vivo human skin colonization assays, based on two biological replicates (Fig. S2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mice infected with wild-type Chicago4 exhibit significant weight loss by day 7, whereas mice infected with Δals4112 do not.

    “Mice infected with the wild-type strain exhibited significant weight loss by day 7, whereas mice infected with the Δals4112 mutant did not (Fig. 6a).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The murine systemic infection model reflects human C. auris systemic infection.

  • May combine two claims.

    Findingown data

    The reduction in fungal burden in the Δals4112 mutant is not due to a growth defect; the mutant displays growth comparable to wild-type and complement strains.

    “The reduction in fungal burden observed in the Δals4112 mutant was not due to a growth defect, as the mutant displayed growth comparable to that of the wild-type and complement strains (Fig. S2B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Iff0675 has more conservation in its repeat sequence than Als4112, but there is more variance in the number of repeats between clades.

    “while the Iff0675 protein has more conservation in its repeat sequence than Als4112, there was more variance in the number of repeats between clades.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    C. auris exhibits strong binding to tropoelastin, collagen V, and laminin.

    “We observed that C. auris exhibited strong binding to tropoelastin, collagen V, and laminin”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ALS4112 and IFF4110 are separated by 4.3 kb, while IFF4110 and IFF4109 are 1.9 kb apart.

    “Specifically, ALS4112 and IFF4110 are separated by 4.3 kb, while IFF4110 and IFF4109 are only 1.9 kb apart.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The complemented strain partially regains virulence, with reduced survival compared to Δals4112 (40% vs. 60%, P = 0.2754).

    “The complemented strain partially regained virulence, resulting in reduced survival compared to the Δals4112 mutant (40% vs. 60%, P = 0.2754) (Fig. 6a).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The murine systemic infection model reflects human C. auris systemic infection.

  • May combine two claims.

    Findingown data

    The Clade III strain B11221 (AR0383) lacks Iff0675 but shows high adherence to keratinocytes.

    “the Clade III strain B11221 (AR0383) lacked Iff0675, but showed high adherence to keratinocytes (Fig. 2c).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.

  • May combine two claims.

    Findingown data

    Iff0675 shows strong conservation in its N- and C-terminal domains, but the number of tandem repeats varies significantly among clades.

    “while Iff0675 also showed strong conservation in its N- and C-terminal domains, the number of tandem repeats varied significantly among clades (Fig. 2g)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The decreased keratinocyte adherence observed for the als4112 mutant aligns with the in vivo murine model, where reduced skin colonization was also evident.

    “Nevertheless, the decreased keratinocyte adherence observed for the als4112 mutant aligns with our in vivo murine model, where reduced skin colonization was also evident.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C. auris adheres to both keratinocytes and ECM proteins found in the skin.

    “Our study demonstrates that C. auris adheres to both keratinocytes and ECM proteins found in the skin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Als4112 is a surface adhesin and the primary mediator of keratinocyte adherence across C. auris clades.

    “Despite the strain-specific variation in keratinocyte adherence, we identified Als4112, a surface adhesin, as the primary mediator of keratinocyte adherence across clades.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    As colonization progresses, C. auris forms a dense layer on the skin surface and penetrates deeper into the tissue, infiltrating the epidermis and extending into the dermis.

    “As colonization progresses, we found that C. auris not only forms a dense layer on the skin surface but also penetrates deeper into the tissue, infiltrating the epidermis and extending into the dermis”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Clinical isolates of all four major clades of C. auris can colonize the skin.

    “While clinical isolates of all four major clades of C. auris can colonize the skin20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Eix, E. F. et al. Ex Vivo human and porcine skin effectively model Candida auris colonization, differentiating robust and poor fungal colonizers. J. Infect. Dis. 225, 1791–1795 (2022). source

  • May combine two claims.

    Interpretationown data

    C. auris adheres to epithelial keratinocytes without activating strong immune responses, and the binding does not depend on host recognition.

    “Our results demonstrate that C. auris adheres to epithelial keratinocytes without activating strong immune responses and that the binding does not depend on host recognition.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.

  • May combine two claims.

    Interpretationown data

    Als4112 is the major adhesin required to mediate keratinocyte adherence across clades, although there is variability between strains on which adhesins are used for binding.

    “Together, these results suggest that Als4112 is the major adhesin required to mediate keratinocyte adherence across clades, although there is variability between strains on which adhesins are used for binding.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.

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

    Interpretationown data

    The variation in adhesion potentially indicates variable selection on C. auris during an outbreak.

    “This variation potentially indicates variable selection on C. auris during an outbreak.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    C. auris binds to specific skin ECM proteins, and Als4112 is a critical factor facilitating the pathogen's interaction with key ECM components in skin tissue.

    “Our findings indicate that C. auris binds to specific skin ECM proteins and highlight Als4112 as a critical factor facilitating the pathogen’s interaction with key ECM components in skin tissue.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Als4112 plays a critical role in C. auris colonization and virulence.

    “Our study highlights the critical role of Als4112 in C. auris colonization and virulence”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    C. auris establishes extensive skin colonization but does not appear to cause overt inflammatory damage.

    “These findings indicate that while C. auris establishes extensive skin colonization, it does not appear to cause overt inflammatory damage.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The murine epicutaneous skin colonization model reflects human C. auris skin colonization.

  • May combine two claims.

    Interpretationown data

    Als4112 is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix proteins, especially laminin.

    “Here, we show that a C. auris conserved adhesin, Als4112, is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix proteins, especially basement membrane proteins such as laminin.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.
    • Rests on an assumption: The murine epicutaneous skin colonization model reflects human C. auris skin colonization.

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

    Premisenone given

    The specific host cells or proteins that C. auris interacts with during skin colonization remain largely unknown, and the exact C. auris factors responsible for binding to host components are yet to be identified.

    “However, the specific host cells or proteins that C. auris interacts with during skin colonization remain largely unknown, and the exact C. auris factors responsible for binding to host components are yet to be identified, underscoring a critical gap in understanding the molecular basis of C. auris skin colonization.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    In Klebsiella pneumoniae, the MrkD adhesin specifically binds to collagen V, enabling adhesion to tubular basement membranes, Bowman's capsule, arterial walls, and the interstitial connective tissues of the kidney.

    “In the bacterial pathogen Klebsiella pneumoniae, the MrkD adhesin specifically binds to collagen V, enabling adhesion to tubular basement membranes, Bowman’s capsule, arterial walls, and the interstitial connective tissues of the kidney54–57.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [54] Sebghati, T. A., Korhonen, T. K., Hornick, D. B. & Clegg, S. Characterization of the type 3 fimbrial adhesins of Klebsiella strains. Infect. Immun. 66, 2887–2894 (1998). source
    • cites [55] Rêgo, A. T. et al. Crystal structure of the MrkD1P receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface. Mol. Microbiol. 86, 882–893 (2012). source
    • cites [56] Tarkkanen, A. M. et al. Type V collagen as the target for type-3 fimbriae, enterobacterial adherence organelles. Mol. Microbiol. 4, 1353–1361 (1990). source
    • cites [57] Tarkkanen, A. M., Westerlund-Wikström, B., Erkkilä, L. & Korhonen, T. K. Immunohistological localization of the MrkD adhesin in the type 3 fimbriae of Klebsiella pneumoniae. Infect. Immun. 66, 2356–2361 (1998). source

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

    Premisecitation

    Many fungal pathogens are known to degrade ECM components as part of their tissue invasion strategy.

    “Many fungal pathogens are known to degrade ECM components as part of their tissue invasion strategy65–68.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [65] Rodrigues, M. L., dos Reis, F. C. G., Puccia, R., Travassos, L. R. & Alviano, C. S. Cleavage of human fibronectin and other basement membrane-associated proteins by a Cryptococcus neoformans serine proteinase. Microb. Pathog. 34, 65–71 (2003). source
    • cites [66] Dos Santos, A. L. & Soares, R. M. Candida guilliermondii isolated from HIV-infected human secretes a 50 kDa serine proteinase that cleaves a broad spectrum of proteinaceous substrates. FEMS Immunol. Med. Microbiol. 43, 13–20 (2005). source
    • cites [67] Pärnänen, P., Kari, K., Virtanen, I., Sorsa, T. & Meurman, J. H. Human laminin-332 degradation by Candida proteinases. J. Oral. Pathol. Med. 37, 329–335 (2008). source
    • cites [68] Pärnänen, P., Meurman, J. H. & Virtanen, I. Laminin-511 and fibronectin degradation with Candida yeast. J. Oral. Pathol. Med. 38, 768–772 (2009). source

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

    Premisecitation

    Among the collagens tested, collagen I, III, and V are classified as fibril-forming collagens, collagen IV forms network structures, and collagen VI forms beaded filaments.

    “Among the collagens tested, collagen I, III, and V are classified as fibril-forming collagens, while collagen IV forms network structures, and collagen VI forms beaded filaments64.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Ricard-Blum, S. The collagen family. Cold Spring Harb. Perspect. Biol. 3, a004978 (2011). source

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

    Premisecitation

    In Escherichia coli, various adhesins from different fimbrial types facilitate binding to host ECM proteins, such as collagens and fibronectin, which contributes to its persistent colonization and infection.

    “In Escherichia coli, various adhesins from different fimbrial types facilitate binding to host ECM proteins, such as collagens and fibronectin, which contributes to its persistent colonization and infection58–62.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [58] Selvarangan, R. et al. Interaction of Dr adhesin with collagen type IV is a critical step in Escherichia coli renal persistence. Infect. Immun. 72, 4827–4835 (2004). source
    • cites [59] Westerlund, B. et al. The O75X adhesin of uropathogenic Escherichia coli is a type IV collagen-binding protein. Mol. Microbiol. 3, 329–337 (1989). source
    • cites [60] Westerlund, B. et al. Multifunctional nature of P fimbriae of uropathogenic Escherichia coli: mutations in fsoE and fsoF influence fimbrial binding to renal tubuli and immobilized fibronectin. Mol. Microbiol. 5, 2965–2975 (1991). source
    • cites [61] Pouttu, R. et al. Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis-associated Escherichia coli to collagens. Mol. Microbiol. 31, 1747–1757 (1999). source
    • cites [62] Farfan, M. J., Inman, K. G. & Nataro, J. P. The major pilin subunit of the AAF/II fimbriae from enteroaggregative Escherichia coli mediates binding to extracellular matrix proteins. Infect. Immun. 76, 4378–4384 (2008). source

  • May combine two claims.

    Study design and conductreasoning

    The keratinocyte model cannot fully capture the spectrum of differentiated keratinocytes, nor the complete array of ECM proteins present in skin tissue.

    “Our keratinocyte model cannot fully capture the spectrum of differentiated keratinocytes, nor the complete array of ECM proteins present in skin tissue.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In Candida albicans, Als3 facilitates adhesion to fibrinogen and collagen IV.

    “In the fungal pathogen, C. albicans, Als3 facilitates adhesion to fibrinogen and collagen IV63.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Nobbs, A. H., Vickerman, M. M. & Jenkinson, H. F. Heterologous expression of Candida albicans cell wall-associated adhesins in Saccharomyces cerevisiae reveals differential specificities in adherence and biofilm formation and in binding oral Streptococcus gordonii. Eukaryot. Cell 9, 1622–1634 (2010). source

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Clade I strains generally exhibit low adherence to keratinocytes.

    “whereas prior reports used Clade I strains, which generally exhibit low adherence to keratinocytes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    The keratinocyte adhesion model remains a useful tool to begin exploring the genetic mechanisms underlying C. auris skin colonization.

    “Thus, the keratinocyte adhesion model remains a useful tool to begin exploring the genetic mechanisms underlying C. auris skin colonization.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The inconsistency between studies on strain-specific variation may be due to the specific strains tested or the use of different models, where variations in skin structure could have influenced the results.

    “This inconsistency may be due to the specific strains tested or the use of different models, where variations in skin structure could have influenced the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    Als4112 is a promising target for vaccination or therapeutic strategies aimed at reducing C. auris skin colonization.

    “further supports Als4112 as a promising target for vaccination or therapeutic strategies aimed at reducing C. auris skin colonization.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The intravenous murine infection procedures were approved by the Institutional Animal Care and Use Committee at the Lundquist Institute at Harbor-UCLA Medical Center (protocol 2022-31988-02).

    “Procedures were approved by the Institutional Animal Care and Use Committee at the Lundquist Institute at Harbor-UCLA Medical Center (protocol 2022-31988-02).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The presence of C. auris on the skin surface and deep in skin tissue may explain its ability to persist and spread in clinical settings, while also increasing the risk of systemic infections.

    “Overall, the presence of C. auris on the skin surface and deep in skin tissue may explain its ability to persist and spread in clinical settings, while also increasing the risk of systemic infections.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The murine epicutaneous colonization procedures were approved by the Institutional Animal Care and Use Committee at the University of Michigan (protocol PRO00011163).

    “Procedures were approved by the Institutional Animal Care and Use Committee at the University of Michigan (protocol PRO00011163).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Unless specified otherwise, all experiments in this study were conducted with a minimum of three independent biological replicates.

    “Unless specified otherwise, all experiments were conducted with a minimum of three independent biological replicates, and data are shown as means ± standard deviation of the means, with each data point representing an individual biological replicate.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Human skin samples used for ex vivo colonization were collected from patients who underwent reconstructive surgeries through an IRB-exempt protocol.

    “Briefly, de-identified samples were collected from patients who underwent reconstructive surgeries through an IRB-exempt protocol, and incubated as described20, with paraffin wax as a barrier between skin surface and media.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The microscopy and photography images shown are representative of at least two experiments that gave similar results.

    “Microscopy and photography images are representative of at least two experiments that showed similar results.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The rat catheter colonization procedures were approved by the Institutional Animal Care and Use Committee at the University of Wisconsin, Madison (protocol MV1947).

    “Procedures were approved by the Institutional Animal Care and Use Committee at the University of Wisconsin, Madison (protocol MV1947).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Each T-DNA integration site in the sequenced mutants was verified by Sanger sequencing.

    “Each T-DNA integration site in the sequenced mutants was verified by Sanger sequencing.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Mutants were confirmed through at least three independent PCR reactions with unique primer sets targeting the mutation site and compared to the parental strains.

    “Mutants were confirmed through at least three independent PCR reactions with unique primer sets targeting the mutation site and compared to the parental strains.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    For deletion mutants, gene-specific primers confirmed the absence of ORF amplification and proper integration of the repair cassette at the correct genomic locus.

    “For deletion mutants, gene-specific primers confirmed the absence of ORF amplification and proper integration of the repair cassette at the correct genomic locus.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The integrity and purity of the RNA were verified using a Nanodrop and by agarose gel electrophoresis before downstream applications.

    “The integrity and purity of the RNA were verified using a Nanodrop and by agarose gel electrophoresis before proceeding to downstream applications.”
    Quote in the paperNot a substantial claim
67 of 67

  • The paper relies on this without support.

    The in vitro keratinocyte adherence model using N/TERT cells reflects C. auris adherence to human skin keratinocytes in vivo.

    “we established an adherence model using the human immortalized keratinocyte cell line (N/TERT)37 to investigate the ability of C. auris to adhere to these cells and assess its requirements for skin colonization.”

  • The paper relies on this without support.

    The murine epicutaneous skin colonization model reflects human C. auris skin colonization.

    “we utilized a murine epicutaneous skin colonization model to examine its distribution on the skin and identify colonization patterns that may contribute to its transmissibility and persistence.”

  • The paper relies on this without support.

    The murine systemic infection model reflects human C. auris systemic infection.

    “Immunosuppressed CD-1 mice were infected with a lethal inoculum of the Chicago4 wild-type strain, the Δals4112 mutant, or the complemented strain and monitored for survival and histopathological changes in primary target organs (kidney and heart).”

  • The paper relies on this without support.

    Overexpression of ALS4112 using the pTEF1 promoter does not alter other genes affecting keratinocyte adherence.

    “we overexpressed ALS4112 in the otherwise low-adherence AR0382 background using the pTEF1 strong constitutive promoter.”

  • The paper relies on this without support.

    The effect of NDV-3A serum on keratinocyte adherence is mediated by antibodies targeting ALS adhesins.

    “IgG from NDV-3A immunized mice binds to C. auris cell surfaces, likely targeting C. auris ALS adhesins30.”

  • The paper relies on this without support.

    Collagen coatings are practical, safe, sustainable, and cost-effective for minimizing C. auris contamination and colonization on medical devices.

    “Our findings offer a practical, safe, sustainable, and cost-effective solution to minimize C. auris contamination and colonization on medical devices, such as catheters.”

  • The paper relies on this without support.

    C. auris persistence on abiotic surfaces in healthcare settings plays a major role in nosocomial outbreaks.

    “This is particularly significant given the persistence of C. auris on abiotic surfaces in healthcare settings, where it plays a major role in nosocomial outbreaks.”

  • The paper relies on this without support.

    The rat central venous catheter model reflects C. auris colonization on human central venous catheters.

    “This pattern was also observed in vivo, where the high-adherent strain AR0383 exhibited an average 6-fold decrease in colonizing the luminal surface of collagen III-coated PE catheters in a rat central venous model compared to uncoated controls (Fig. 7e).”

  • The paper relies on this without support.

    No sex bias has been observed in the murine epicutaneous C. auris colonization model.

    “Experiments were conducted using female mice as no sex bias has been observed in this model, thus reducing extraneous use of animals.”

  • The paper relies on this without support.

    No sex bias has been observed in the intravenous murine C. auris infection model.

    “Experiments were conducted using male mice as no sex bias has been observed in this model, thus reducing the extraneous use of animals.”
10 of 10

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • C. auris can invade the deeper dermis, a feature not previously observed among human commensal yeasts.

    “C. auris can invade the deeper dermis, a feature not previously observed among human commensal yeasts [3,11].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [11]

    The Results (Als4112 facilitates C. auris colonization of host skin; page not provided) report that C. auris penetrated deep into the dermis in a murine skin model. The Discussion says skin invasion was not reported in previous C. auris studies, but it does not establish that dermal invasion had never been observed among human commensal yeasts. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • C. auris strains belonging to clade III highly express SCF1 and ALS4112, associated with greater adherence capacity.

    “C. auris strains belonging to clade III highly express SCF1 and ALS4112, associated with greater adherence capacity.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [11]

    The Results section, “Modulating ALS4112 expression levels regulates C. auris adherence to keratinocytes” (page unavailable), reports that ALS4112 expression correlates with keratinocyte adherence across isolates, regardless of clade. The Results section, “Als4112 is the major adhesin mediating keratinocyte adherence” (page unavailable), identifies one highly adherent Clade III strain, but does not establish that Clade III strains generally highly express ALS4112 or SCF1. The Discussion (page unavailable) says SCF1 deletion did not reduce adherence in the keratinocyte assay; the claimed joint expression pattern is therefore not supported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Clade II had low expression of SCF1 and ALS4112, and exhibited low adherence capacity.

    “On the other hand, clade II had low expression of SCF1 and ALS4112, and exhibited low adherence capacity.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [11]

    The Results section on ALS4112 expression (page unavailable) reports a positive correlation between ALS4112 transcript abundance and keratinocyte adhesion across isolates, and the keratinocyte-adherence section reports variation between clades. It does not state that Clade II specifically had low ALS4112 or SCF1 expression or low adherence; its mention of SCF1 in the Discussion concerns skin colonization, not Clade II expression. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • Among C. auris clinical isolates, the magnitude of ALS4112 expression correlated with their keratinocyte adherence capacity, with Clade IV exhibiting comparatively higher adherence.

    “Concordantly, among C. auris clinical isolates, the magnitude of ALS4112 expression correlated with their keratinocyte adherence capacity, with Clade IV exhibiting comparatively higher adherence.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [11]

    The Results section, “Modulating ALS4112 expression levels regulates C. auris adherence to keratinocytes” (page unavailable), reports a strong positive correlation between ALS4112 transcript abundance and keratinocyte adherence across 33 isolates. The Results also identify Chicago4 as a highly adherent Clade IV strain, but report substantial variation within and between clades; they do not establish that Clade IV isolates generally have higher adherence than other clades. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Strains belonging to clades I and IV uncoordinatedly express SCF1 and ALS4112, with regulation independent among the individual strains.

    “Furthermore, strains belonging to clades I and IV uncoordinatedly express SCF1 and ALS4112, with regulation independent among the individual strains.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [11]

    The Results section, “Modulating ALS4112 expression levels,” reports variation in ALS4112 transcript abundance among clinical isolates across clades. The Discussion mentions Scf1, but our copy does not compare its expression with ALS4112 or establish independent, strain-specific regulation of the two genes. No page numbers were provided for these passages. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(1, 31) = 38.46reported p < .0001 · recomputed p < .001

    “F(1, 31) = 38.46, p < .0001”

1 of 1

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.

  • Adhesion-screen Z-score has the opposite sign from its selection rule

    Minor

    The stated formula subtracts each mutant's adhesion proportion from the plate average, so a mutant with reduced adhesion would have a positive Z-score. The screen instead selects negative Z-scores as reduced-adhesion mutants, affecting how its candidates were identified.

1 of 1

Cites

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Cited by

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Related

Authors
Zhao, G., Lyu, J., Veniaminova, N. A., Zarnowski, R., Mattos, E., Johnson, C. J., Quintanilla, D., Hautau, H., Hold, L. A., Xu, B., Anku, J. A. E., Dasgupta, K., Hale, J. J., Steltzer, S. S., Santana, D. J., Ibrahim, A. S., Snitkin, E. S., Andes, D., Nett, J. E., Singh, S., Abraham, A. C., Killian, M. L., Kahlenberg, J. M., Wong, S. Y., & O’Meara, T. R.
Affiliations
  • University of Michigan (US)
  • University of California, Los Angeles (US)
  • University of Wisconsin–Madison (US)
Corresponding author
O’Meara, Teresa R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-07-01
Volume
16
Issue
1
Pages
5673-5673
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-60876-1
PMC
PMC12214902
OpenAlex
W4411886860
Semantic Scholar
5778c7a145b15d20df0913098beed9759ccc9736
Cited by
32
References
83
Citations by year
2026: 28 · 2025: 4
FWCI
22.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Health Research Alliance (cc-by)
Funders
  • American Heart Association (938451)
  • National Institutes of Health (5t32ai007413-32, 1f32ai181164-01, T32 AI00,7413, P30-AR069620, AR069620, R01AR065409, R01AI145939, KL2TR001882, 4r01ai073289-17, 2k24ar076975-06)
  • National Institute of Allergy and Infectious Diseases (T32-AI-007413, F32 AI181164, U19 AI181767, F31AI169823, R01 AI145939, R21 AI169186, K01AI180591)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24‐AR076975, R01AR065409, P30AR069620, R01AR080654)
  • National Center for Advancing Translational Sciences (KL2TR001882)
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, adhesins, skin colonization, keratinocytes, extracellular matrix, laminin, basement membrane, fungal adhesion, biofilm formation, collagen coating, nosocomial transmission, virulence
MeSH terms
Candida auris, Animals, Candidiasis, Cell Adhesion, Disease Models, Animal, Female, Fungal Proteins, Humans, Laminin, Skin, Virulence, Keratinocytes, Extracellular Matrix Proteins, Biofilms, Mice

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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