PgmNr Y3184: Rme1 controls chlamydospore formation in the human pathogenic yeast Candida albicans.

Authors:
A. Hernandez Cervantes 1,2 ; S. Znaidi 1,2 ; V. Basso 1,2 ; F. Vincent 3 ; F. Dalle 3 ; M. E. Bougnoux 1,2 ; N. Sertour 1,2 ; S. Bachellier-Bassi 1,2 ; C. d’Enfert 1,2


Institutes
1) Pasteur Institute, Paris, France; 2) INRA, USC2019, F-75015 Paris, France; 3) UMR 1347, Agroécologie AgroSup/INRA/uB 21065 Dijon, France.


Keyword: Other Yeasts

Abstract:

Candida albicans is the most common pathogenic fungus of humans, normally found as a harmless commensal colonizing skin and mucosal epithelium of 30-70% healthy individuals. This yeast causes systemic infections in the absence of a proper immune system, by gaining access to the bloodstream mainly through translocation across the intestinal barrier. A characteristic of this organism is its capability to react to variations of the environment by growing either as unicellular yeasts or in filamentous forms (true hyphae or pseudohyphae). The ability to switch between yeast and filaments is a virulence trait, important for the success of C. albicans both as a commensal and as a pathogen. Upon specific growth conditions, C. albicans can produce chlamydospores, which are large refractile cells with thick cell walls, often forming on suspensor cells attached to hyphae, neither dead nor long-term survival cells, likely to be a specialized and alternative form of growth of C. albicans. Previous studies in our laboratory suggested that the C. albicans transcription factor Rme1, ortholog of Saccharomyces cerevisiae regulator of meiosis, was involved in the yeast-hyphae transition. In order to determine the in vivo function of Rme1, we performed ChIP-on-chip and transcriptomics analyses on an inducible overexpression (OE) strain, showing that Rme1 binds to 724 promoter regions, upregulating 622 genes and downregulating 357 genes. The most strongly upregulated genes are markers of chlamydospore development. To explore the role of Rme1 in this morphogenetic program, RME1 OE and knock-out (KO) mutant strains were grown on Potato Carrot Bile Agar medium under microaerophilic conditions in the dark for 7 days. The OE strain formed masses of chlamydospores as compared to the SC5314 wild type strain, whereas the KO strain was unable to form these structures. Moreover, we observed that the expression levels of RME1 and its targets were increased in C. albicans clinical isolates that overproduced chlamydospores. In addition, we observed that RME1 OE could restore the defect in chlamydospore development displayed by the hog1ΔΔ and efg1ΔΔ  KO strains, suggesting that Rme1 acts as a bottleneck regulator in the chlamydospore formation pathway. Taken together, our results confirm that the function of ScRme1 in the regulation of meiosis has been lost in C. albicans and has been rewired towards the control of a complex regulatory network necessary for chlamydospore formation.



Yeast Database Genetic Index
1. gene symbol: RME1; systematic name: C1_07330W_A