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Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence
et la résistance aux antifongiques chez la levure
Candida albicans

Abstract : Ambient pH signaling involves a cascade of conserved Rim or Pal products in ascomycetous yeasts or
filamentous fungi, respectively. Recent evidences in the fungi Aspergillus nidulans, Saccharomyces cerevisiae,
Yarrowia lipolytica, and Candida albicans suggested that components of endosomal sorting complexes required
for transport (ESCRT) involved in endocytic trafficking were needed for signal transduction along the Rim
pathway. In this study, we confirm these findings with C. albicans and show that Vps28p (ESCRT-I) and
Vps32p/Snf7p (ESCRT-III) are required for the transcriptional regulation of known targets of the Rim
pathway, such as the PHR1 and PHR2 genes encoding cell surface proteins, which are expressed at alkaline and
acidic pH, respectively. We additionally show that deletion of these two VPS genes, particularly VPS32, has a
more drastic effect than a RIM101 deletion on growth at alkaline pH and that this effect is only partially
suppressed by expression of a constitutively active form of Rim101p. Finally, in an in vivo mouse model, both
vps null mutants were significantly less virulent than a rim101 mutant, suggesting that VPS28 and VPS32 gene
products affect virulence both through Rim-dependent and Rim-independent pathways.
Vps28p and Vps32p act in both the endocytic and the pH signaling pathways in yeasts and are required for
Candida albicans virulence. Here, we show that deletions of VPS28 and VPS32 increase the susceptibility of C.
albicans to cell wall disruption agents, echinocandin and azole antifungal agents.
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Submitted on : Thursday, April 26, 2007 - 12:10:47 PM
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  • HAL Id : tel-00143611, version 1
  • PRODINRA : 251786

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Citation

Murielle Gigou-Cornet. Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence
et la résistance aux antifongiques chez la levure
Candida albicans. Biochimie [q-bio.BM]. INAPG (AgroParisTech), 2006. Français. ⟨NNT : 2006INAP0037⟩. ⟨tel-00143611⟩

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