The Candida auris Hog1 MAP kinase is essential for the colonization of murine skin and systemic infection
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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 |
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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: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 is essential for efficient skin colonization, intradermal persistence as well as systemic virulence. RNA-seq analysis of wild-type parental and hog1Δ mutant strains revealed marked downregulation of genes involved in processes such as cell adhesion, cell wall rearrangement, and pathogenesis in hog1Δ mutant compared to the wild-type parent. Consistent with these data, we found a prominent role for Hog1 in maintaining cell wall architecture, as the hog1Δ mutant demonstrated a significant increase in cell-surface β-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.ImportanceCandida auris is a World Health Organization fungal priority pathogen and an urgent public health threat recognized by the Centers for Disease Control and Prevention. C. auris has a unique ability to colonize human skin. It also persists on abiotic surfaces in healthcare environments for an extended period of time. These attributes facilitate the inter- and intrahospital clonal transmission of C. auris. Therefore, understanding C. auris skin colonization mechanisms is critical for infection control, especially in hospitals and nursing homes. However, despite its profound clinical relevance, the molecular and genetic basis of C. auris skin colonization mechanisms are poorly understood. Herein, we present data on the identification of the Hog1 MAP kinase as a key regulator of C. auris skin colonization. These findings lay the foundation for further characterization of unique mechanisms that promote fungal persistence on human skin.
| S-EPMC11558994 | biostudies-literature
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:Employing 4D label-free proteomics, we explored the contributions of acetylome alterations to the evolution of fluconazole resistance in C. auris. From 18 samples of six C. auris strains, we identified 2,419 acetylated proteins with 7,833 sites, quantified 2,032 proteins and 6,310 sites.
2025-04-22 | PXD058801 | 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: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:To mimic the initial phases of systemic Candida infections with dissemination via the bloodstream, we used an ex vivo whole blood infection model. Dual TP of C. auris in blood gave insights into fungal adaptations and survival mechanisms as well as the host response to the infection.
2022-01-12 | GSE179000 | GEO
Project description:Candida auris is a recently found pathogenic yeast that causes systemic infections, showing a high mortality rate. The delay on making a correct diagnosis of C. auris is a current problem in the healthcare system setting. As immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies, in this study immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris, and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The aim was to identify the most immunoreactive antigens of this yeast. Thirteen spots were recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry. They corresponded to enolase, phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase and phosphoglycerate mutase. These four proteins seem to be also recognized by sera obtained from human patients with disseminated C. auris infection, but not by sera obtained from mice infected with other fungi such as C. albicans or Aspergillus fumigatus. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.
2024-06-23 | PXD049077 | Pride
Project description:Yeast Hog1-3HA ChIP-Chip in triplicate Keywords: ChIP-Chip
2006-05-26 | GSE4862 | GEO
Project description:Yeast Hog1-3HA ChIP-Chip in triplicate Keywords: ChIP-Chip Yeast Hog1 ChIP-Chip was performed in MAP51 (3HA-Hog1) in triplicate using anti-HA (12CA5 monoclonal antibody)
2010-07-01 | E-GEOD-4862 | biostudies-arrayexpress