Role of RIM and VPS genes in pH signaling, virulence and resistance to antifungal drugs in the yeast Caandida albicans ; Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence et la résistance aux antifongiques chez la levure Candida albicans

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. ; Résumé Candida albicans est le premier pathogène fongique de l'homme. Cette levure, habituellement commensale, peut être à l'origine d'infections profondes mettant en jeu le pronostic vital. L'incidence des candidoses profondes ne cesse d'augmenter parallèlement à l'augmentation du nombre de patients à risque. La virulence de C. albicans s'explique par sa capacité à coloniser puis envahir de nombreux tissus de l'organisme qui constituent autant de microenvironnements différents. Les ...