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Multiple genes of Candida albicans influencing echinocandin susceptibility in caspofungin-adapted mutants

ABSTRACT: Expression profiles of five caspofungin adapted candida albicans strains were analysed from their parental strains

ORGANISM(S): Candida albicans

PROVIDER: GSE217094 | GEO | 2022/11/05

REPOSITORIES: GEO

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Multiple genes of Candida albicans influencing echinocandin susceptibility in caspofungin-adapted mutants

Project description:Multiple genes of Candida albicans influencing echinocandin susceptibility in caspofungin-adapted mutants

| PRJNA896937 | ENA

Multiple Genes of Candida albicans Influencing Echinocandin Susceptibility in Caspofungin-Adapted Mutants.

Project description:Candida albicans is an opportunistic human fungal pathogen that causes invasive infections in immunocompromised individuals. Despite the high anticandidal activity among the echinocandins (ECNs), a first-line therapy, resistance remains an issue. Furthermore, many clinical isolates display decreased ECN susceptibility, a physiological state which is thought to lead to resistance. Determining the factors that can decrease susceptibility is of high importance. We searched for such factors genome-wide by comparing the transcriptional profiles of five mutants that acquired decreased caspofungin susceptibility in vitro in the absence of canonical FKS1 resistance mutations. The mutants were derived from two genetic backgrounds and arose due to independent mutational events, some with monosomic chromosome 5 (Ch5). We found that the mutants exhibit common transcriptional changes. In particular, all mutants upregulate five genes from Ch2 in concert. Knockout experiments show that all five genes positively influence caspofungin and anidulafungin susceptibility and play a role in regulating the cell wall mannan and glucan contents. The functions of three of these genes, orf19.1766, orf19.6867, and orf19.5833, were previously unknown, and our work expands the known functions of LEU42 and PR26. Importantly, orf19.1766 and LEU42 have no human orthologues. Our results provide important clues as to basic mechanisms of survival in the presence of ECNs while identifying new genes controlling ECN susceptibility and revealing new targets for the development of novel antifungal drugs.

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Project description:Approximately 200 cells of Candida albicans lab strain SC5314 were spread on YPD plates supplemented with 2 fold increase from 50 ng/ml to 12800ng/ml caspofungin. All adaptors appeared were collected. Randomly 36 tolerant adaptors were sequenced.

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Transcriptome profile of tra1 mutant in C. albicans in response to the antifungal caspofungin

Project description:The emergence of drug-resistant fungal strains is a threat to human health. Identifying targets that increase the susceptibility of fungal pathogens to current therapies will significantly improve outcomes. Tra1 is an essential component of the SAGA and NuA4 transcriptional co-activator complexes and is linked to multiple cellular processes associated with the yeast response to antifungal drugs. This submission contains RNA sequencing data from Candida albicans strain expressing a Tra1 mutant with three arginine to glutamine mutations in the PI3K domain (tra1Q3; Berg et al., 2018) treated with or without the antifungal caspofungin. Our goal was to identify genes regulated by Tra1 in C. albicans and identify genes with differential responses in the mutant tra1 strain upon capsofungin relative to the wild-type strain. We identified 68 genes that were differentially expressed when the tra1Q3 strain was treated with caspofungin, as compared to gene expression changes induced by either tra1Q3 or caspofungin alone. Included in this set were genes involved in cell wall maintenance, adhesion and filamentous growth. As a critical component of both SAGA and NuA4, Tra1 is uniquely positioned to regulate the yeast antifungal response and emerges, through targeting its PI3K domain, as a promising new therapeutic target for fungal infections.

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Gcn5 Controls Virulence of the Human Fungal Pathogen Candida albicans through Multiple Regulatory Networks

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Whole genome sequencing of caspofungin adaptors derived from homozygous deletion strains of PKC and calcineurin pathways in Candida albicasn

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Whole genome sequencing of caspofungin adaptors in Candida albicans

Project description:Whole genome sequencing of caspofungin adaptors in Candida albicans

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Whole genome sequencing of fluconazole tolerant adaptors derived from exposure to echinocandins in Candida albicans

Project description:Candida albicans lab strain SC5314 was spread on YPD plates supplemented with echinocandins (caspofungin, anidulafungin, micafungin, rezafungin). The adaptors were tested for tolrance to fluconazole. Randomly 43 tolerant adaptors, as well as the parent SC5314, were sequenced.

2023-07-11 | E-MTAB-12449 | biostudies-arrayexpress

Response of Candida albicans to taurocholate

Project description:Presence of taurocholate (TC), a constituent of bile, confers resistance of Candida albicans to antifungals like Caspofungin and Amphotericin B. Transcriptional profiles in presence and absence of TC were compared to determine whether an upregulation of known resistance genes is responsible for this effect. No upregulation was found, and the resistance seemed to be rather based on a direct interaction of TC with the antifungals.

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