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Cited by 116Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris

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Day, Alison M., McNiff, Megan M., da Silva Dantas, Alessandra, Gow, Neil A. R., Quinn, Janet·2018·mSphere
DOI 10.1128/msphere.00506-18PMC PMC6200985
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Abstract

The rapid global emergence and resistance of Candida auris to current antifungal drugs highlight the importance of understanding the virulence traits exploited by this human fungal pathogen to cause disease. Here, we characterize the stress resistance profile of C. auris and the role of the Hog1 stress-activated protein kinase (SAPK) in stress resistance and virulence. Our findings that C. auris is acutely sensitive to certain stresses may facilitate control measures to prevent persistent colonization in hospital settings. Furthermore, our observation that the Hog1 SAPK promotes C. auris virulence akin to that reported for many other pathogenic fungi indicates that antifungals targeting Hog1 signaling would be broad acting and effective, even on emerging drug-resistant pathogens.

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  • Clinical features of C. auris infections include biofilm persistence on abiotic surfaces and skin, immune evasion, and antifungal drug resistance.

    “The clinical features of these infections include biofilm persistence on abiotic surfaces and skin, immune evasion, and antifungal drug resistance (7–12).”

    From Dual function of <i>Candida auris</i> mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [7]

    The Introduction reports antifungal drug resistance, biofilm formation, persistent colonization of hospital wards and patients, and evasion of neutrophil-mediated killing. The Discussion notes detection on skin. Neither passage establishes that biofilms themselves persist on abiotic surfaces and skin, so that specific part of the claim is unsupported. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • C. auris Hog1 has previously been reported to be important for antifungal drug resistance, stress response, and virulence in a Caenorhabditis elegans model of infection.

    “The C. auris Hog1 has previously been reported to be important for antifungal drug resistance, stress response, and was also shown to be important for virulence in a Caenorhabditis elegans model of infection (39, 40).”

    From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [39]

    The Results sections on stress resistance and virulence report that Hog1 protects C. auris against several stresses and that deleting it attenuates virulence in a C. elegans infection model. The antifungal-drug claim needs qualification: the functional-characterization Results report greater caspofungin resistance in cells lacking Hog1, while the stress-resistance Results find Hog1 dispensable for fluconazole resistance. The paper does not establish that Hog1 promotes antifungal drug resistance generally. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Hog1 confers resistance to osmotic, cationic, acid, and reactive oxygen species-induced stress.

    “Specifically, Hog1 confers resistance to osmotic, cationic, acid, and reactive oxygen species-induced stress [75,76].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [75]

    The Results section ('Hog1-mediated stress resistance in C. auris') reports that cells lacking Hog1 were sensitive to osmotic and cationic stress, H2O2, and highly acidic conditions. The claim omits important limits: Hog1 was dispensable in moderately acidic conditions and for resistance to the organic oxidative stress-inducing agent tert-butyl hydroperoxide, so the findings do not establish resistance to acid or reactive oxygen species-induced stress generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The stress responses studied by Day and colleagues involved the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK).

    “Despite the different profiles, these responses involved the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK).”

    From Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin (2020) · cites this paper as [22]

  • Day and colleagues showed that C. auris exhibited a unique stress resistance profile compared to other Candida spp.

    “However, studies by Day and colleagues characterized the responses of Candida to a variety of stresses, including high salinity, and showed that C. auris exhibited a unique stress resistance profile compared to those of other Candida spp. (22).”

    From Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin (2020) · cites this paper as [22]

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References 61 · Cited by 116

Research works printed but not linked: 51

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Authors
Day, A. M., McNiff, M. M., da Silva Dantas, A., Gow, N. A. R., & Quinn, J.
Affiliations
  • Newcastle University (GB)
  • MRC Centre for Medical Mycology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
  • University of Aberdeen (GB)
Corresponding author
  • Day, Alison M.
  • Quinn, Janet
ORCID
Venue
mSphere
Publisher
American Society for Microbiology
Published
2018-10-31
Volume
3
Issue
5
ISSN
2379-5042 (ISSN-L)
DOI
10.1128/msphere.00506-18
PMC
PMC6200985
OpenAlex
W2896989720
Cited by
116
References
61
Citations by year
2026: 14 · 2025: 20 · 2024: 18 · 2023: 19 · 2022: 10 · 2021: 13 · 2020: 14 · 2019: 8
FWCI
6.62
Type
journal article
Language
en
Open access
Licence
Locations
  • mSphere (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (097377, 101873)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/K016393/1, BB/P020119/1)
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, Hog1, c-Jun N-terminal kinase, stress tolerance, virulence, antifungal resistance, emerging fungal pathogens, hospital colonization, antifungal drug targets, fungal pathogenesis
MeSH terms
Adaptation, Physiological, Animals, Candida, Candidiasis, Fungal Proteins, Moths, Stress, Physiological, Virulence, Mitogen-Activated Protein Kinases, Mice, Host-Pathogen Interactions

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