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Loss of mitochondrial functions in Candida glabrata results in enhanced virulence in mice

ABSTRACT: Two C. glabrata related isolates recovered from the same patient undergoing azole therapy were characterized. The first isolate, BPY40, is azole-susceptibleand the second, BPY41, is azole-resistant. To determine whether the petite mutation conferred a selective advantage during host infection, the virulence of BPY40 and BPY41 was assessed in mice. Surprisingly, the petite mutant, even if showing in vitro growth deficiency as compared to BPY40, was more virulent than BPY40 both in intravenous and vaginal murine infection models. The increased virulence of the petite mutant correlated with a drastic gain of fitness in mice as compared to its parental isolate. Genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction. Finally, some genes involved in cell wall genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction.

ORGANISM(S): Nakaseomyces glabratus CBS 138 Nakaseomyces glabratus

PROVIDER: GSE23826 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA130561

REPOSITORIES: GEO

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Loss of mitochondrial functions in Candida glabrata results in enhanced virulence in mice

Project description:Two C. glabrata related isolates recovered from the same patient undergoing azole therapy were characterized. The first isolate, BPY40, is azole-susceptibleand the second, BPY41, is azole-resistant. To determine whether the petite mutation conferred a selective advantage during host infection, the virulence of BPY40 and BPY41 was assessed in mice. Surprisingly, the petite mutant, even if showing in vitro growth deficiency as compared to BPY40, was more virulent than BPY40 both in intravenous and vaginal murine infection models. The increased virulence of the petite mutant correlated with a drastic gain of fitness in mice as compared to its parental isolate. Genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction. Finally, some genes involved in cell wall genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction. Gene expression was measured in 2 related C. glabrata clinical isolates (BPY40 and BPY41). The one-color system was used . 3 independent experiments were performed using 3 biological replicate for each strain.

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