Dataset Information

Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negative Candida species

ABSTRACT: we performed mitochondrial proteomic analysis on multiple Candida species (C. albicans, C. glabrata, C. krusei and Candida auris) and analyzed the differentially expressed mitochondrial proteins (DEMPs) between azole-sensitive and azole-resistant Candida species.

ORGANISM(S): Fungal Sp. Nt-01

SUBMITTER: Xiaodong She

PROVIDER: PXD045101 | iProX | Tue Sep 05 00:00:00 BST 2023

REPOSITORIES: iProX

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Publications

Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negative Candida species.

Zhou Meng M Peng Jingwen J Ren Kun K Yu Yu Y Li Dongmei D She Xiaodong X Liu Weida W

Microbiology spectrum 20240305 4

Azole drugs are the main therapeutic drugs for invasive fungal infections. However, azole-resistant strains appear repeatedly in the environment, posing a major threat to human health. Several reports have shown that mitochondria are associated with the virulence of pathogenic fungi. However, there are few studies on the mechanisms of mitochondria-mediated azoles resistance. Here, we first performed mitochondrial proteomic analysis on multiple Candida species (Candida albicans, ...[more]

PMID: 38442003

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Project description:Although Candida albicans and Candida dubliniensis are most closely related, both species significantly behave differently with respect to morphogenesis and virulence. In order to gain further insight into the divergent routes for morphogenetic adaptation in both species, we investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. Following genome-associated assembly of sequence reads we were able to generate experimentally verified databases containing 6016 and 5972 genes for C. albicans and C. dubliniensis, respectively. About 95% of the transcriptionally active regions (TARs) contain open reading frames while the remaining TARs most likely represent non-coding RNAs. Comparison of our annotations with publically available gene models for C. albicans and C. dubliniensis confirmed approximately 95% of already predicted genes, but also revealed so far unknown novel TARs in both species. Qualitative cross-species analysis of these databases revealed in addition to 5802 orthologs also 399 and 49 species-specific protein coding genes for C. albicans and C. dubliniensis, respectively. Furthermore, quantitative transcriptional profiling using RNA-Seq revealed significant differences in the expression of orthologs across both species. We defined a core subset of 84 hyphal-specific genes required for both species, as well as a set of 42 genes that seem to be specifically induced during hyphal morphogenesis in C. albicans. Species specific adaptation in C. albicans and C. dubliniensis is governed by individual genetic repertoires but also by altered regulation of conserved orthologs on the transcriptional level. We investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. In a first step, we reevaluated the in silico predicted gene models by collecting experimental data using FLX - technology for sequencing strand-specific and normalized cDNA libraries derived from blastospores and hyphae. In the second step, quantitative RNA-Seq (GAIIX) was applied to C. albicans hyphal cells and C. dubliniensis blastospore and hyphal cells to complement reevaluation of the gene models with FLX data as well as to measure differential gene expression across the species with two biological replicates.

Dataset Information

Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negative Candida species

Publications

Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negative <i>Candida</i> species.

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