The Candida auris Hog1 MAP kinase is essential for the colonization of murine skin and systemic infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1079743 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28114548_1.fastq.gz | Fastqsanger.gz | |||
| SRR28114548_2.fastq.gz | Fastqsanger.gz | |||
| SRR28114549_1.fastq.gz | Fastqsanger.gz | |||
| SRR28114549_2.fastq.gz | Fastqsanger.gz | |||
| SRR28114550_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Candida auris, a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic C. auris infections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that C. auris, unlike most Candida species, displays unique skin tropism and can stay on human skin for a prolonged period. However, the molecular mechanisms responsible for C. auris skin colonization, intradermal persistence, and systemic virulence are poorly understood. Here, we report that C. auris Hog1 mitogen-activated protein kinase (MAPK) is essential for efficient skin colonization, intradermal persistence, as well as, systemic virulence. RNA-seq analysis of wildtype parental and hog1D mutant strains from YPD-grown cultures revealed marked down-regulation of genes involved in processes such as cell adhesion, cell-wall rearrangement, and pathogenesis in hog1D mutant compared to the wildtype parent. In agreement, we found a prominent role for Hog1 in maintaining cell-wall architecture, as the hog1D mutant demonstrated a significant increase in cell-surface b-glucan exposure and a concomitant reduction in chitin content. Additionally, we observed that Hog1 was required for biofilm formation in vitro and fungal survival when challenged with primary murine macrophages and neutrophils ex vivo. Collectively, these findings have important implications for understanding the C. auris skin adherence mechanisms and penetration of skin epithelial layers preceding bloodstream infections.
2024-10-02 | GSE256470 | GEO
Project description: Not available
| S-EPMC11558994 | biostudies-literature
Project description:Candida auris is an emerging multidrug-resistant fungus that has sparked public health alarm. However, the mechanisms supporting its persistence in skin, a major risk factor for deadly outbreaks, remain unclear. Here, we compared skin colonization by C. auris with that of the related pathobiont C. albicans, illuminating fungal–immune interactions. C. auris exhibited enhanced skin persistence, tropism to hair follicles, and direct binding to hair. Whereas C. albicans triggered a type 3/17-skewed sterilizing antifungal immune response, C. auris triggered a type 1 IFNg-driven response directed toward hair follicles. IFNg unexpectedly enhanced C. auris colonization through direct signaling to keratinocytes, impairing barrier integrity and repressing antifungal defense programs. Genetic and biochemical approaches demonstrated that, in response to skin-associated cues, C. auris upregulates the exposure of cell wall chitin, which is sufficient to trigger type 1 immunity and benefit the pathobiont.
2026-08-10 | GSE328064 | GEO
Project description:Candida auris (C. auris) is an emerging fungal pathogen with a remarkable ability to persist on human skin, but how structural skin cells respond to colonization is unclear. We used ex vivo human skin models, primary keratinocytes and fibroblasts to characterize epithelial and stromal responses to C. auris compared with Candida albicans (C. albicans). C. auris formed biofilms and induced a wound-model-dependent pattern of cytokine secretion dominated by IL-1β and IL-6, yet caused minimal epithelial damage and modest reductions in leukocyte viability. RNA sequencing revealed complementary but cell-type-specific responses. Keratinocytes and fibroblasts both amplified a pro-inflammatory IL-6/CXCL8 response, while keratinocytes additionally upregulated antimicrobial genes such as RNASE7, TSLP, DEFB103A, and the neutrophil-recruiting chemokines CXCL2 and CXCL3. Fibroblasts further induced CCL28, supporting T-cell recruitment, alongside transcriptional programs associated with tissue remodeling. Recombinant RNase 7 and short form TSLP directly inhibited C. auris growth in vitro in a dose-dependent manner. Together, these findings identify keratinocytes as epithelial sentinels that integrate inflammatory and antimicrobial defenses against skin-tropic C. auris and suggest that fibroblast-driven cytokine amplification and especially antimicrobial peptides from within the skin barrier may provide therapeutic targets to limit C. auris skin colonization.
2026-06-12 | GSE334767 | GEO
Project description:Candida auris is an emerging multidrug-resistant fungus that has sparked public health alarm. However, the mechanisms supporting its persistence in skin, a major risk factor for deadly outbreaks, remain unclear. Here, we compared skin colonization by C. auris with that of the related pathobiont C. albicans, illuminating fungal–immune interactions. C. auris exhibited enhanced skin persistence, tropism to hair follicles, and direct binding to hair. Whereas C. albicans triggered a type 3/17-skewed sterilizing antifungal immune response, C. auris triggered a type 1 IFNg-driven response directed toward hair follicles. IFNg unexpectedly enhanced C. auris colonization through direct signaling to keratinocytes, impairing barrier integrity and repressing antifungal defense programs. Genetic and biochemical approaches demonstrated that, in response to skin-associated cues, C. auris upregulates the exposure of cell wall chitin, which is sufficient to trigger type 1 immunity and benefit the pathobiont.
2026-08-10 | GSE329153 | GEO
Project description:Candida auris is an emerging multidrug-resistant fungus that has sparked public health alarm. However, the mechanisms supporting its persistence in skin, a major risk factor for deadly outbreaks, remain unclear. Here, we compared skin colonization by C. auris with that of the related pathobiont C. albicans, illuminating fungal–immune interactions. C. auris exhibited enhanced skin persistence, tropism to hair follicles, and direct binding to hair. Whereas C. albicans triggered a type 3/17-skewed sterilizing antifungal immune response, C. auris triggered a type 1 IFNg-driven response directed toward hair follicles. IFNg unexpectedly enhanced C. auris colonization through direct signaling to keratinocytes, impairing barrier integrity and repressing antifungal defense programs. Genetic and biochemical approaches demonstrated that, in response to skin-associated cues, C. auris upregulates the exposure of cell wall chitin, which is sufficient to trigger type 1 immunity and benefit the pathobiont.
2026-08-10 | GSE328701 | GEO
Project description:In this study, we designed a novel antifungal agent, PQA-Az-13 that demonstrated antifungal activity against C. auris biofilms. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes and characterized by biophysical and spectral techniques. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models.
2023-12-07 | PXD046911 | Pride
Project description:The stress-activated protein kinase Hog1 is best known for its role in osmotic stress but is also activated by a variety of mechanistically distinct environmental stressors including heat shock, ER stress, and arsenic. In the osmotic stress response, the signal is sensed upstream and relayed to Hog1 via a kinase cascade. Here we identify a novel mode of Hog1 function whereby Hog1 senses arsenic though direct physical interaction requiring three conserved cysteine residues located adjacent to the catalytic loop. These residues are essential for Hog1's role in protecting against arsenic, but completely dispensable for osmotic stress, and mediate Hog1's cellular localization upon arsenic exposure. Hog1 in turn regulates arsenic detoxification by phosphorylating the transcription factor Yap8, promoting its nuclear localization, and stimulating transcription of its only known targets, Arr2 and Arr3, which promote arsenic efflux. Arsenic binding was also observed with the related human kinases Erk1 and Erk2, suggesting that this may be a conserved aspect of this kinase family. These data provide a mechanistic basis for understanding how stress-activated kinases can sense individual threats and carry out highly specific adaptive responses.
2019-12-04 | PXD015325 | Pride
Project description:Based on studies in S. pombe (Chen et al., 2003), we predicted that conditions which activate C. albicans Hog1 would result in the induction of a common set of genes that are regulated by this SAPK (Smith et al., 2004). Hence in this study we compared the global transcriptional responses of wild-type and hog1 C. albicans cells to environmental stresses that are known to activate the Hog1 SAPK. We compared the homozygous hog1/hog1 null mutant (JC50) with the isogenic HOG1 reintegrant (hog1/hog1/HOG1: JC52) because this controlled for any secondary mutations that might have been introduced during the construction of the null mutant. We have shown that this reintegrant is indistinguishable from its parental wild-type strain RM1000 (HOG1/HOG1) with respect to their stress phenotypes (Smith et al., 2004) and their expression of stress genes (Supplementary Data). Three conditions were chosen for transcript profiling: osmotic stress imposed by 0.3 M NaCl, oxidative stress imposed by 5 mM H2O2, and heavy metal stress imposed by 0.5 mM CdSO4. Each of these treatments stimulates the phosphorylation and nuclear accumulation of this Hog1 SAPK within a 10-min time frame (Smith et al., 2004). Furthermore, significant differences in stress regulated gene expression are observed within this time scale (Enjalbert et al., 2003; Smith et al., 2004). Hence, we analyzed the C. albicans transcriptome after a 10-min exposure to each stress condition. Although some stress genes might be missed by analyzing a single time point, most C. albicans stress genes are induced within 10 min (Enjalbert et al., 2003). At least four independent biological replicates were analyzed for each condition
2007-07-05 | E-MEXP-1134 | biostudies-arrayexpress
Project description:Yeast Hog1-3HA ChIP-Chip in triplicate Keywords: ChIP-Chip
2006-05-26 | GSE4862 | GEO