Project description:Investigation of whole genome gene expression level changes in Candida glabrata CBS138 delta-vph2 mutant, compared to the wild-type strain in SC broth (pH5.0 and pH7.4). VPH2 gene encodes a protein that is the assembly factor of a functional V-ATPase. Loss of Vph2p leads to loss of a functional V-ATPase enzyme complex.
Project description:Candida glabrata is an important human fungal pathogen leading cause of non-albicans Candida infections. C. glabrata exhibits resistance to key antifungal drugs, rapidly replicates and divides in host macrophages and withstands highly stressful host conditions. This study explores the molecular mechanisms underlying stress adaptations in C. glabrata that contribute to its pathogenicity. Our findings revealed that C. glabrata survives oxidative stress and amino acid starvation more effectively than S. cerevisiae, C. albicans, and C. auris. We noted that Gcn2 kinase and Gcn4 play critical roles in this adaptation as Gcn2 phosphorylates eIF2α and downregulates the global protein translation, activating GCN4. RNA sequencing of WT and gcn4 mutant revealed that GCN4 activation during stress orchestrates the expression of stress-responsive genes vital for survival during amino acid starvation and oxidative stress. Ultimately assisting in the stress adaptative transcriptome. Thus, this study highlights the critical role of the Gcn2–Gcn4 pathway in stress adaptation in C. glabrata.
Project description:Pdr1 is the major regulator of azole resistance in the fungal pathogen Candida glabrata. Earlier experiments demonstrated that expression of Pdr1 itself is increased when cells lose their mitochondrial genome (rho0). Here we use chromatin immunoprecipitation coupled with highthroughput sequencing (ChIP-seq) to map the genomic binding sites for Pdr1 in both normal and rho0 cells. These data provide the first look at genes that are likely to represent the direct targets of Pdr1 in this important pathogen.