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Cited by 13Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

Yeast and filamentous Candida auris stimulate distinct immune responses in the skin

Open access
Bryak, Garrett, Cox, Abigail, Lionakis, Michail S., Thangamani, Shankar·2024·mSphere
DOI 10.1128/msphere.00055-24PMC PMC11288036
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Abstract

Candida auris , an emerging multidrug-resistant fungal pathogen, predominately colonizes the human skin long term leading to subsequent life-threatening invasive infections. Fungal morphology is believed to play a critical role in modulating mucocutaneous antifungal immunity. In this study, we used an intradermal mouse model of C. auris infection to examine fungal colonization and the associated innate and adaptive immune response to yeast and filamentous C. auris strains. Our results indicate that mice infected with a filamentous C. auris had significantly decreased fungal load compared to mice infected with the yeast form. Mice infected with yeast and filamentous forms of C. auris stimulated distinct innate immune responses. Phagocytic cells (CD11b + Ly6G + neutrophils, CD11b + Ly6C hi inflammatory monocytes, and CD11b + MHCII + CD64 + macrophages) were differentially recruited to mouse skin tissue infected with yeast and filamentous C. auris . The percentage and absolute number of interleukin 17 (IL-17) producing innate lymphoid cells, TCRγδ + , and CD4 + T cells in the skin tissue of mice infected with filamentous C. auris were significantly increased compared to the wild-type of yeast strain. Furthermore, complementation of filamentous mutant strain of C. auris (Δ elm1 + ELM1 ) strain exhibited wild-type yeast morphology in vivo and induced comparable level of skin immune responses similar to mice infected with yeast strain. Collectively, our findings indicate that yeast and filamentous C. auris induce distinct local immune responses in the skin. The decreased fungal load observed in mouse skin infected with filamentous C. auris is associated with a potent IL-17 immune response induced by this morphotype. IMPORTANCE: Candida auris is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other Candida species, C. auris predominantly colonizes and persists in skin tissue resulting in outbreaks of systemic infections. Understanding the factors that regulate C. auris skin colonization and host immune response is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We identified that yeast and filamentous forms of C. auris induce distinct skin immune responses in the skin. These findings may help explain the differential colonization and persistence of C. auris morphotypes in skin tissue. Understanding the skin immune responses induced by yeast and filamentous C. auris is important to develop novel vaccine strategies to combat this emerging fungal pathogen.

AI snapshot

Written from the paper’s full text.

TL;DR

In an intradermal mouse model, filamentous *Candida auris* (Δelm1) produced lower skin fungal burden and distinct innate/adaptive immune responses compared with yeast-form wild-type *C. auris*. The lower burden was associated with a more potent IL-17 response, while complementation restored WT-like morphology and immune responses.

Key findings

  • Filamentous Δelm1-infected skin had significantly lower fungal load than WT yeast at 3 and 14 days: 6.41 ± 0.56 vs 7.42 ± 0.69 log10 CFU/g at 3 days, and 5.34 ± 0.48 vs 6.14 ± 0.53 log10 CFU/g at 14 days; complement Δelm1 + ELM1 values were 6.89 ± 0.64 and 6.21 ± 0.55 log10 CFU/g, respectively.
  • Phagocytic cells were differentially recruited: Δelm1 increased the percentage but not absolute number of CD11b+Ly6G+ neutrophils, while decreasing both percentage and absolute number of CD11b+Ly6Chi inflammatory monocytes and CD11b+MHCII+CD64+ macrophages compared with WT.
  • Δelm1 induced stronger IL-17 responses: percentages of IL-17A/IL-17F-producing ILCs, TCRγδ+, TCRβ+, and CD4+ T cells were significantly increased versus WT, with significant absolute increases for IL-17A+ ILCs, TCRγδ+, TCRβ+, CD4+, and IL-17F+TCRγδ+ and CD4+ T cells; CD8+ T cells showed no significant differences.
  • The complemented Δelm1 + ELM1 strain exhibited WT yeast morphology in vivo and induced skin immune responses comparable to WT.

Methods

  • Generated a filamentous *C. auris* mutant by CRISPR-Cas9-mediated deletion of *ELM1* in WT South Asian AR0387 and a complemented Δelm1 + ELM1 strain; confirmed by PCR and sequencing.
  • Used an intradermal mouse model in 6–8-week-old female and male C57BL/6J mice; assessed fungal burden by CFU/g and qPCR, histopathology by PAS staining, and immune cells by flow cytometry.
  • Analyzed phagocytes (neutrophils, inflammatory monocytes, macrophages) and IL-17A/IL-17F-producing ILCs, TCRγδ+, TCRβ+, CD4+, and CD8+ T cells; statistics used Mann-Whitney U test with n = 8–10 mice per group.

Limitations

  • Stated: future studies using different clades of *C. auris* clinical strains are required; this study used one South Asian AR0387 isolate.
  • Evident: findings are from an intradermal mouse model only, with assessments at 3 and 14 days post-infection, and the proposed role of cell wall composition differences was not directly tested.
  • Evident: the text reports the inoculum as 1–2 × 10^6 CFU in the results and 1–2 × 10^7 CFU in the methods, an inconsistency in the provided paper.

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

Integrity signals

Registry

Crossref · 10.1128/msphere.00055-24

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

22 of 25 cited sources checked · 13 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms.

    “Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms (8–14).”
    Quote in the paperSubstantial claim5 of 7 sources checked
    • cites [8] Santana DJ, O’Meara TR. 2021. Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains. Nat Commun 12: 7197. doi: 10.1038/s41467-021-27545-5 34893621 PMC8664941 source

      The Introduction (page not provided) describes C. auris cellular polymorphism, including pseudohyphal cells induced by stress, filamentous strains recovered after murine infection, and aggregating patient isolates. The Results section on ELM1 (page not provided) describes wild-type budding yeast morphology. Together these support the range of forms, but the paper does not establish that clinical isolates exhibit all three forms as stated without those experimental or infection-related conditions. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [9] Fan S, Yue H, Zheng Q, Bing J, Tian S, Chen J, Ennis CL, Nobile CJ, Huang G, Du H. 2021. Filamentous growth is a general feature of Candida auris clinical isolates. Med Mycol 59: 734– 740. doi: 10.1093/mmy/myaa116 33485272 PMC8257410 source
    • cites [10] Brown JL, Delaney C, Short B, Butcher MC, McKloud E, Williams C, Kean R, Ramage G. 2020. Candida auris phenotypic heterogeneity determines pathogenicity in vitro. mSphere 5: e00371-20. doi: 10.1128/mSphere.00371-20 32581078 PMC7316489 source

      The Materials and Methods describe single-celled and aggregative C. auris clinical isolates, and the Discussion says hyphal formation can be induced under some conditions. But the Discussion attributes a yeast-to-pseudohyphae-to-hyphae transition to C. albicans, not C. auris; it also notes that C. auris structures observed on porcine skin lacked pseudohyphae and hyphae. The paper therefore does not support the full list of morphotypes attributed to C. auris clinical isolates. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [11] Du H, Bing J, Hu T, Ennis CL, Nobile CJ, Huang G. 2020. Candida auris: epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog 16: e1008921. doi: 10.1371/journal.ppat.1008921 33091071 PMC7581363 source
    • cites [12] Seiser S, Arzani H, Ayub T, Phan-Canh T, Staud C, Worda C, Kuchler K, Elbe-Bürger A. 2024. Native human and mouse skin infection models to study Candida auris-host interactions. Microbes Infect 26: 105234. doi: 10.1016/j.micinf.2023.105234 37813159 source
    • cites [13] Yue H, Bing J, Zheng Q, Zhang Y, Hu T, Du H, Wang H, Huang G. 2018. Filamentation in Candida auris, an emerging fungal pathogen of humans: passage through the mammalian body induces a heritable phenotypic switch. Emerg Microbes Infect 7: 188. doi: 10.1038/s41426-018-0187-x 30482894 PMC6258701 source
    • cites [14] Bravo Ruiz G, Ross ZK, Gow NAR, Lorenz A. 2020. Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint. mSphere 5: e00151-20. doi: 10.1128/mSphere.00151-20 32161147 PMC7067593 source
  • Premisecitation

    Skin immune responses to C. auris are different from C. albicans.

    “Furthermore, recent findings from our laboratory suggest that skin immune responses to C. auris are different from C. albicans (4).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Datta A, Das D, Nett JE, Vyas JM, Lionakis MS, Thangamani S. 2023. Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans. Microbiol Spectr 11: e0221523. doi: 10.1128/spectrum.02215-23 37811989 PMC10848846 source
  • Interpretationcitation

    Yeast and filamentous forms of C. auris and C. albicans induce different immune responses in the skin.

    “Our findings along with others (15) suggest that yeast and filamentous forms of C. auris and C. albicans induce different immune responses in the skin.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.
    • Rests on an assumption: The C. auris AR0387 strain is representative of clinical C. auris isolates for the purpose of generalizing the findings.
  • Premisecitation

    Fungal colonization was significantly higher in mice skin infected with yeast form of C. auris 0387 strain compared to mice infected with wild-type C. albicans SC5314 which can exist as both yeast and hyphal forms.

    “Recent findings from our lab along with others indicate that fungal colonization was significantly higher in mice skin infected with yeast form of C. auris 0387 strain compared to mice infected with wild-type C. albicans SC5314 which can exist as both yeast and hyphal forms (3, 4).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [3] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. 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. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Results section, “Candida auris Persistently Colonizes Skin” (page not available), reports that C. auris colonized wild-type mouse ear skin consistently, whereas C. albicans colonized it minimally. But it says the NIH C. auris isolate was used in most experiments and does not establish that the direct skin comparison used strain 0387 or that the difference was statistically significant. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [4] Datta A, Das D, Nett JE, Vyas JM, Lionakis MS, Thangamani S. 2023. Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans. Microbiol Spectr 11: e0221523. doi: 10.1128/spectrum.02215-23 37811989 PMC10848846 source

      The Results section (page unavailable) reports significantly higher skin fungal loads in mice infected intradermally with C. auris AR0387 than with C. albicans SC5314 at days 3 and 14. The cited paper identifies both strains, but the passages in our copy do not establish the claim’s additional descriptions of AR0387 as yeast-form or SC5314 as wild-type and capable of both yeast and hyphal forms. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    C. auris persists in murine skin for several months.

    “Emerging evidence suggests that C. auris persists in murine skin for several months (3).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. 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. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source
  • May combine two claims. 13
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Premisecitation

    C. auris has a unique ability to colonize and persist in human skin long term resulting in nosocomial transmission.

    “Unlike other Candida species such as Candida albicans that colonize the mammalian gastrointestinal tract, C. auris has a unique ability to colonize and persist in human skin long term resulting in nosocomial transmission (3–6).”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [3] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. 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. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Introduction states that C. auris can colonize patients’ skin for months and describes this persistence as unusual among Candida species. It says skin and environmental persistence likely contribute to nosocomial transmission, but does not establish that long-term skin colonization itself results in transmission, as the claim implies. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [4] Datta A, Das D, Nett JE, Vyas JM, Lionakis MS, Thangamani S. 2023. Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans. Microbiol Spectr 11: e0221523. doi: 10.1128/spectrum.02215-23 37811989 PMC10848846 source
    • cites [5] Proctor DM, Drummond RA, Lionakis MS, Segre JA. 2023. One population, multiple lifestyles: commensalism and pathogenesis in the human mycobiome. Cell Host Microbe 31: 539– 553. doi: 10.1016/j.chom.2023.02.010 37054674 PMC10155287 source
    • cites [6] Proctor DM, Dangana T, Sexton DJ, Fukuda C, Yelin RD, Stanley M, Bell PB, Baskaran S, Deming C, Chen Q, Conlan S, Park M, Welsh RM, Vallabhaneni S, Chiller T, Forsberg K, Black SR, Pacilli M, Kong HH, Lin MY, Schoeny ME, Litvintseva AP, Segre JA, Hayden MK, NISC Comparative Sequencing Program. 2021. Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility. Nat Med 27: 1401– 1409. doi: 10.1038/s41591-021-01383-w 34155414 PMC9396956 source

  • May combine two claims.

    Premisecitation

    Individuals colonized with C. auris can develop a high fungal burden on their skin, which is positively correlated with environmental contamination, transmission, and outbreaks of systemic infections.

    “Individuals who have been colonized with C. auris can develop a high fungal burden on their skin, which has been positively correlated with environmental contamination, transmission, and outbreaks of systemic infections (7).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Sexton DJ, Bentz ML, Welsh RM, Derado G, Furin W, Rose LJ, Noble-Wang J, Pacilli M, McPherson TD, Black S, Kemble SK, Herzegh O, Ahmad A, Forsberg K, Jackson B, Litvintseva AP. 2021. 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. doi: 10.1093/cid/ciab327 33978150 PMC8492228 source

      The Results section (page not provided) reports that skin colonization burden was positively associated with contamination of residents’ bed handrails. The Discussion says colonized residents can carry high skin burdens, but the study does not establish a positive correlation between skin burden and transmission or outbreaks of systemic infections. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    C. albicans yeast but not filament-locked mutant strain induces a potent Th17 immune response in the mouse skin.

    “Furthermore, C. albicans yeast but not filament-locked mutant strain induces a potent Th17 immune response in the mouse skin (15).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source

  • May combine two claims.

    Premisecitation

    ELM1 is a regulator of C. auris morphology, where disruption of this gene results in filamentation.

    “ELM1 is a regulator of C. auris morphology, where disruption of this gene results in filamentation (8).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Santana DJ, O’Meara TR. 2021. Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains. Nat Commun 12: 7197. doi: 10.1038/s41467-021-27545-5 34893621 PMC8664941 source

  • May combine two claims.

    Findingown data

    WT C. auris AR0387 strain exists as a typical round-shaped yeast form, whereas deletion of ELM1 gene (Δelm1) resulted in an elongated, filamentous morphology.

    “As expected, we identified that WT C. auris AR0387 strain exists as a typical round-shaped yeast form, whereas deletion of ELM1 gene (Δelm1) resulted in an elongated, filamentous morphology which is consistent with previous findings (Fig. 1A) (8).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Santana DJ, O’Meara TR. 2021. Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains. Nat Commun 12: 7197. doi: 10.1038/s41467-021-27545-5 34893621 PMC8664941 source

      The Results section, “ELM1 is a regulator of C. auris filamentous growth” (page unavailable), reports budding-yeast morphology in wild-type cells and elongated, filament-like growth after ELM1 deletion. But those experiments used AR0382 and AR0381, not the claimed AR0387 strain; the copy does not establish this morphology change in AR0387. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Fungal morphology plays a critical role in regulating colonization, virulence, and immune response in different host niches including the skin.

    “Previous findings in other Candida species suggest that fungal morphology plays a critical role in regulating the colonization, virulence, and immune response in different host niches including the skin (15).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source

      The Introduction (page unavailable) links the yeast-to-hypha transition to virulence and describes different forms at the skin surface and in deeper tissues. The Introduction and Abstract report morphology-dependent immune responses and tissue-specific protection. The paper does not establish that morphology regulates colonization, so that part of the claim is not supported. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Candida auris is an emerging multidrug-resistant fungal pathogen that poses a serious threat to public health.

    “Candida auris is an emerging multidrug-resistant fungal pathogen that poses a serious threat to public health.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [1] Ahmad S, Alfouzan W. 2021. Epidemiology, diagnosis, pathogenesis, antifungal susceptibility, and infection control measures to combat the spread of infections in healthcare facilities. Microorganisms 9: 807. doi: 10.3390/microorganisms9040807 33920482 PMC8069182 source
    • cites [2] WHO. 2022. WHO fungal priority pathogens list to guide research, development and public health action. Geneva World Health Organization. https://iris.who.int/bitstream/handle/10665/363682/9789240060241-eng.pdf?sequence=1.

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Mouse skin infected with WT strain features the yeast form, whereas mice infected with Δelm1 exhibited pseudohyphae/filamentous fungal forms at 3 days and 14 days post-infection.

    “Our results indicate that mouse skin infected with the WT strain features the yeast form, whereas mice infected with Δelm1 exhibited pseudohyphae/filamentous fungal forms at 3 days and 14 days post-infection (Fig. 1B).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • May combine two claims.

    Findingown data

    The percentage but not the absolute number of CD11b+Ly6G+ neutrophils was significantly increased in mouse skin tissue infected with Δelm1 compared to WT.

    “We found that the percentage but not the absolute number of CD11b+Ly6G+ neutrophils was significantly increased in the mouse skin tissue infected with the Δelm1 strain compared to WT C. auris-infected groups (Fig. 1D).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • May combine two claims.

    Findingown data

    The percentage and absolute number of neutrophils, monocytes, and macrophages in mice skin infected with Δelm1 + ELM1 were comparable to WT, as no significance was observed.

    “The percentage and absolute number of neutrophils, monocytes, and macrophages in mice skin infected with Δelm1 + ELM1 were comparable to WT, as no significance was observed between these strains (Fig. 1D and E).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • May combine two claims.

    Findingown data

    IL-17 responses in mice skin infected with Δelm1 + ELM1 were comparable to WT, as no significance was observed.

    “IL-17 responses in mice skin infected with Δelm1 + ELM1 were comparable to WT, as no significance was observed between these strains (Fig. 2D and E).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • May combine two claims.

    Findingown data

    The percentage and absolute number of CD11b+Ly6Chi monocytes and CD11b+MHCII+CD64+ macrophages were significantly decreased in skin tissue of mice infected with Δelm1 compared to WT.

    “On the other hand, the percentage and absolute number of CD11b+Ly6Chi monocytes and CD11b+MHCII+CD64+ macrophages were significantly decreased in the skin tissue of mice infected with the Δelm1 strain (Fig. 1E and F).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • May combine two claims.

    Findingown data

    The absolute numbers of IL-17A+ILCs, IL-17A+TCRγδ+, IL-17A+TCRβ+, IL-17A+CD4+, IL-17F+TCRγδ+, and IL-17F+CD4+ T cells were significantly increased in skin tissue of Δelm1-infected mice compared to WT.

    “Moreover, the absolute numbers of IL-17A+ILCs, IL-17A+TCRγδ+ IL-17A+TCRβ+, IL-17A+CD4+, IL-17F+TCRγδ+, and IL-17F+CD4+ T cells were significantly increased in the skin tissue of Δelm1-infected mice compared to WT groups (Fig. 2A through D).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.
    • Rests on an assumption: The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisecitation

    C. albicans predominately exists as a yeast form on the stratum corneum of the skin, while pathogenic pseudohyphal and filamentous forms of C. albicans exist in the dermis.

    “For example, C. albicans predominately exists as a yeast form on the stratum corneum of the skin, while pathogenic pseudohyphal and filamentous forms of C. albicans exist in the dermis.”
    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

    Microscopic examination was performed by a board-certified veterinary pathologist, and the interpretation was based on standard histopathological morphology.

    “Microscopic examination was performed by a board-certified veterinary pathologist, and the interpretation was based on standard histopathological morphology.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All animal studies were approved by the Institutional Animal Care and Use Committee at Purdue University.

    “All animal studies were approved by the Institutional Animal Care and Use Committee at Purdue University.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The gene deletion was confirmed by PCR and sequencing.

    “We confirmed the gene deletion by PCR and sequencing (Fig. S1; Table S1).”
    Quote in the paperSubstantial claim
17 of 17

  • The paper relies on this without support.

    The differences in skin immune responses between WT and Δelm1 C. auris are due to filamentous morphology rather than other effects of ELM1 deletion.

    “Collectively, our findings indicate that yeast and filamentous C. auris induce distinct local immune responses in the skin.”

  • The paper relies on this without support.

    The intradermal mouse model of C. auris infection is a valid model for human skin colonization and immune responses.

    “In this study, we used an intradermal mouse model of C. auris infection to examine fungal colonization and the associated innate and adaptive immune response to yeast and filamentous C. auris strains.”

  • The paper relies on this without support.

    The C. auris AR0387 strain is representative of clinical C. auris isolates for the purpose of generalizing the findings.

    “The Candida auris strain used in this study is the South Asian AR0387 isolate sourced from the CDC AR Isolate Bank, USA.”
3 of 3

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?

  • Clinical isolates of C. auris can exhibit different morphotypes, such as yeast, filamentous, and aggregative forms.

    “Clinical isolates of C. auris can exhibit different morphotypes, such as yeast, filamentous, and aggregative forms (9–13).”

    From Cell aggregation mediated by <i>ACE2</i> deletion in <i>Candida auris</i> modulates fungal colonization and host immune responses in the skin (2024) · cites this paper as [13]

    The OBSERVATION section says clinical isolates can have yeast and filamentous forms, but its list names pseudohyphal—not aggregative—forms as the third example. The searched passages provide no support for the aggregative part of the claim; page numbers are unavailable in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Clinical isolates of C. auris exhibit distinct morphologies, including yeast, aggregative, and filamentous.

    “Clinical isolates of C. auris exhibit distinct morphologies, including yeast, aggregative, and filamentous [104–108].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [108]

    The OBSERVATION section (page not provided) says clinical isolates can exhibit yeast and filamentous forms, alongside pseudohyphal forms. It does not identify an aggregative morphotype, so that item in the cited list is not supported by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The murine skin model is widely used to study disease pathogenesis and C. auris-host interactions.

    “In addition, understanding the skin immune responses against C. auris is critical, as the murine skin model is widely used to study disease pathogenesis and C. auris-host interactions [4, 16–20].”

    From Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris (2024) · cites this paper as [19]

Cites

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Authors
Bryak, G., Cox, A., Lionakis, M. S., & Thangamani, S.
Affiliations
  • Purdue University West Lafayette (US)
  • National Institutes of Health (US)
ORCID
Venue
mSphere
Publisher
American Society for Microbiology
Published
2024-07-30
Volume
9
Issue
7
Pages
e0005524-e0005524
ISSN
2379-5042 (ISSN-L)
DOI
10.1128/msphere.00055-24
PMC
PMC11288036
OpenAlex
W4399889588
Semantic Scholar
0d3e9c172cbd4c8476ff0c8389340714856d1b01
Cited by
13
References
25
Citations by year
2026: 7 · 2025: 3 · 2024: 3
FWCI
4.10
Type
journal article
Language
en
Open access
Licence
Locations
  • mSphere (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (1R01AI177604)
  • HHS | NIH | NIAID | Division of Intramural Research (ZIA AI001175)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida auris, skin colonization, antifungal immunity, innate immune response, IL-17, innate lymphoid cells, TCR gamma delta T cells, CD4+ T cells, neutrophils, inflammatory monocytes, macrophages, fungal morphology, intradermal infection, multidrug-resistant fungi
MeSH terms
Candida auris, Animals, Candidiasis, Disease Models, Animal, Female, Immunity, Innate, Mice, Inbred C57BL, Skin, Interleukin-17, Mice, Adaptive Immunity

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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