Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris

Day, Alison M.; Mcniff, Megan M; Dantas, Alessandra da Silva; Gow, Neil A. R.; Quinn, Janet

doi:10.1128/msphere.00506-18

Cited by 77 publications

(103 citation statements)

References 61 publications

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

Section: Discussionmentioning

confidence: 99%

Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin

Horton

Johnson

Kernien

et al. 2020

mSphere

115

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Emerging pathogen Candida auris causes nosocomial outbreaks of lifethreatening invasive candidiasis. It is unclear how this species colonizes skin and spreads in health care facilities. Here, we analyzed C. auris growth in synthetic sweat medium designed to mimic axillary skin conditions. We show that C. auris demonstrates a high capacity for biofilm formation in this milieu, well beyond that observed for the most commonly isolated Candida sp., Candida albicans. The C. auris biofilms persist in environmental conditions expected in the hospital setting. To model C. auris skin colonization, we designed an ex vivo porcine skin model. We show that C. auris proliferates on porcine skin in multilayer biofilms. This capacity to thrive in skin niche conditions helps explain the propensity of C. auris to colonize skin, persist on medical devices, and rapidly spread in hospitals. These studies provide clinically relevant tools to further characterize this important growth modality. IMPORTANCE The emerging fungal pathogen Candida auris causes invasive infections and is spreading in hospitals worldwide. Why this species exhibits the capacity to transfer efficiently among patients is unknown. Our findings reveal that C. auris forms high-burden biofilms in conditions mimicking sweat on the skin surface. These adherent biofilm communities persist in environmental conditions expected in the hospital setting. Using a pig skin model, we show that C. auris also forms high-burden biofilm structures on the skin surface. Identification of this mode of growth sheds light on how this recently described pathogen persists in hospital settings and spreads among patients.

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Section: Discussionmentioning

confidence: 99%

Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin

Horton

Johnson

Kernien

et al. 2020

mSphere

115

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“…Additional indirect support for the role of cell morphology and structure in the different, clade-specific C. auris phenotypes described here comes from recent studies involving deletion of the evolutionarily conserved stress-activated protein kinase Hog1. Perturbation of the hog1 gene in C. auris isolates induced the formation of large cellular aggregates/clumps; increased resistance to cell wall-damaging agents, including the echinocandins; an increased exposure of chitin on the cell surface; and notably, a significant reduction in virulence in vivo (46). Further studies will be required to evaluate whether C. auris isolates from the different clades exhibit differences in Hog1 activity or activation profiles or differential interactions between Hog1 and associated mitogen-activated protein kinase pathways.…”

Section: Discussionmentioning

confidence: 99%

Candida auris Isolates of the Southern Asian and South African Lineages Exhibit Different Phenotypic and Antifungal Susceptibility Profiles In Vitro

2019

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Candida auris is a serious nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Sequence analyses of outbreak isolates revealed that C. auris has simultaneously emerged as four distinct continentally restricted clonal lineages. We previously reported multiple independent introductions of C. auris isolates from at least three of these lineages (the Southern Asia, South African, and Japanese/Korean lineages) into hospitals across the United Kingdom and that isolates circulating in the United Kingdom displayed two different cell phenotypes which correlated with differences in virulence in Galleria mellonella wax moths. Here, we compared the phenotypic characteristics and antifungal susceptibilities of isolates representative of the three geographic clades circulating in the United Kingdom. Isolates of the South African and Japanese/Korean lineages, but not those of the Southern Asian lineage, grew well on media containing actidione. However, unlike Southern Asian lineage isolates, they were unable to produce even rudimentary pseudohyphae in culture. Importantly, although all isolates were fluconazole resistant in vitro, fluconazole and voriconazole exhibited significantly higher MICs against isolates of the South African lineage than against isolates of the Southern Asian lineage. A similar trend was seen with minimum fungicidal concentrations (MFCs), with higher MFCs of the triazole antifungal agents being seen for the South African lineage isolates. Finally, the formation of large cellular aggregates was seen only with isolates of the South African and Japanese/Korean lineages, which correlates with the reduced virulence observed previously in Galleria wax moths inoculated with such isolates. Intriguingly, aggregation could be reversibly induced in isolates of the Southern Asian lineage by exposure to triazole and echinocandin antifungals but not by exposure to amphotericin B or flucytosine.

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“…Recent evidence has demonstrated that the stress-activated protein kinase Hog1 plays an evolutionarily conserved role in C. auris stress resistance, cell wall homeostasis, and virulence (Day et al, 2018). C. auris Hog1 shares 87% identity with the C. albicans Hog1 sequence.…”

Section: Stress Resistance and Persistencementioning

confidence: 99%

Nine Things Genomics Can Tell Us About Candida auris

2020

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Candida auris is a recently emerged multidrug-resistant fungal pathogen causing severe illness in hospitalized patients. C. auris is most closely related to a few environmental or rarely observed but cosmopolitan Candida species. However, C. auris is unique in the concern it is generating among public health agencies for its rapid emergence, difficulty to treat, and the likelihood for further and more extensive outbreaks and spread. To date, five geographically distributed and genetically divergent lineages have been identified, none of which includes isolates that were collected prior to 1996. Indeed, C. auris' ecological niche(s) and emergence remain enigmatic, although a number of hypotheses have been proposed. Recent genomic and transcriptomic work has also identified a variety of gene and chromosomal features that may have conferred C. auris with several important clinical phenotypes including its drug-resistance and growth at high temperatures. In this review we discuss nine major lines of enquiry into C. auris that big-data technologies and analytical approaches are beginning to answer.

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Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris

Cited by 77 publications

References 61 publications

Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin

Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin

Candida auris Isolates of the Southern Asian and South African Lineages Exhibit Different Phenotypic and Antifungal Susceptibility Profiles In Vitro

Nine Things Genomics Can Tell Us About Candida auris

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