Fungal Biology and Pathogenicity - INRA USC2019  


  HEADD’ENFERT Christophe, PhD / denfert@pasteur.fr
  MEMBERSBACHELLIER-BASSI Sophie, PhD / BONHOMME Julie, MD / BOUGNOUX Marie-Elisabeth, MD PhD / CABRAL Vitor / CHAUVEL Murielle / DIOGO Dorothée / LEGRAND Mélanie, PhD / NESSEIR Audrey / ROSSIGNOL Tristan, PhD / SDOUDI Karima / ZEIDLER Ute, PhD


  Annual Report

Fungal infections represent a significant, and yet poorly controlled, part of nosocomial infections. The Fungal Biology and Pathogenicity Unit is studying three aspects of the biology of Candida albicans, a diploid and polymorphic yeast responsible for the vast majority of opportunistic fungal infections in humans.

Genetic diversity of Candida albicans

Our work in collaboration with Aberdeen University has resulted in the identification of 5 major and 12 minor phylogenetic groups (clades) structuring the C. albicans population. Current research is aimed at investigating at a genomic level the extent of the genetic diversity that distinguishes isolates within or between clades. Our results have shown that microevolutions of diploid C. albicans within clades are frequently mediated by loss-of-heterozygosity (LOH) events (chromosome losses or large mitotic recombination events). Yet, these large LOH events appear counter-selected in the C. albicans population. The mechanisms that regulate LOH are being investigated at the molecular level. We are now using deep-sequencing in order to characterize genetic diversity of C. albicans isolates from various clades at the whole-genome level.

Biofilm formation by Candida albicans

Biofilms are microbial communities that develop in association with a biotic or abiotic surface. They form a protected environment where micro-organisms adopt a specific physiology. Candida biofilm cells have an elevated resistance to antifungals and this often results in sequels following an apparently successful antifungal treatment. Functional analysis of C. albicans genes over-expressed upon biofilm formation has confirmed that the yeast-to-hypha transition is critical for biofilm formation and has identified genes necessary for biofilm cohesiveness, in particular a regulator of glycolysis that is essential for adaptation to the hypoxic environment occurring within biofilms. Our recent results suggest that antifungal resistance of biofilms might be mainly mediated by entrapment of the antifungals in extracellular matrix materials, especially glucans.

Regulation of morphogenesis

Morphogenesis is central to the virulence of C. albicans. We have shown that the C. albicans Yak1 kinase regulates hyphal emergence and maintenance. Through the establishment of a partial C. albicans ORFeome and the implementation of an over-expresion screen we have recently uncovered novel regulators of morphogenesis that, together with Yak1, are being investigated using a variety of post-genomics approaches (transcriptomics, ChIP-Seq, phosphoproteomics, suppressor screens). Importantly, our laboratory has recently been funded together with Aberdeen University to establish the complete C. albicans ORFeome and an exhaustive collection of C. albicans over-expression strains. This will represent the first academic resource for functional genomics in C. albicans.

Keywords: Candida albicans, biofilm, antifungal resistance, epidemiology, candidemia, candidosis, cell wall proteins, kinase, signaling



  Publications

Diogo, D., C. Bouchier, C. d'Enfert & M. E. Bougnoux, (2009) Loss of heterozygosity in commensal isolates of the asexual diploid yeast Candida albicans. Fungal Genet Biol 46: 159-168. (19059493)

Enjalbert, B., A. Rachini, G. Vediyappan, D. Pietrella, R. Spaccapelo, A. Vecchiarelli, A. J. Brown & C. d'Enfert, (2009) A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections. Infect Immun 77: 4847-4858. (19687206)

Moreno-Ruiz, E., M. Galan-Diez, W. Zhu, E. Fernandez-Ruiz, C. d'Enfert, S. G. Filler, P. Cossart & E. Veiga, (2009) Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11: 1179-1189. (19416270)

Goyard, S., P. Knechtle, M. Chauvel, A. Mallet, M. C. Prevost, C. Proux, J. Y. Coppee, P. Schwartz, F. Dromer, H. Park, S. G. Filler, G. Janbon & C. d'Enfert, (2008) The Yak1 kinase is involved in the initiation and maintenance of hyphal growth in Candida albicans. Mol Biol Cell 19: 2251-2266. (18321992)

Firon, A., S. Aubert, I. Iraqui, S. Guadagnini, S. Goyard, M. C. Prevost, G. Janbon & C. d'Enfert, (2007) The SUN41 and SUN42 genes are essential for cell separation in Candida albicans. Mol Microbiol 66: 1256-1275. (18001349)

Odds, F. C., M. E. Bougnoux, D. J. Shaw, J. M. Bain, A. D. Davidson, D. Diogo, M. D. Jacobsen, M. Lecomte, S. Y. Li, A. Tavanti, M. C. Maiden, N. A. Gow & C. d'Enfert, (2007) Molecular phylogenetics of Candida albicans. Euk cell 6: 1041-1052. (17416899)



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