Fungal Biology and Pathogenicity - INRA USC2019  


  HEADDr. D’ENFERT Christophe / denfert@pasteur.fr
  MEMBERSABELANET Sophie / Dr. BOUGNOUX Marie-Elisabeth / CHAUVEL Murielle / DIOGO Dorothée / Dr. FIRON Arnaud / Dr. LESIC Biliana / NESSEIR Audrey / Dr. ROSSIGNOL Tristan / Dr. VEDIYAPPAN Govindsamy


  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

We have established C. albicans Multi Locus Sequence Typing (MLST) and applied it to clinical and commensal C. albicans strains. In collaboration with Aberdeen University, we have shown that almost all of 1400 C. albicans isolates can be assigned by MLST to one of 17 clades and that C. albicans animal isolates show some separation from human isolates.

Current research in this field 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 environment. 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. We have shown that several of these genes play a role in cell wall architecture. Our recent results suggest that antifungal resistance of biofilms might be mainly mediated by entrapment of the antifungals in extracellular matrix materials.

Protein kinases and regulation of morphogenesis

Morphogenesis is central to the virulence of C. albicans. We have shown that the C. albicans C. albicans ORFeome and the implementation of an over-expresion screen we have recently uncovered novel regulators of morphogenesis that are currently being investigated.

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



  Publications

Bougnoux, M.E., Pujol, C., Diogo, D., Bouchier, C., Soll, D.R. and d'Enfert, C. (2008) Mating is rare within as well as between clades of the human pathogen Candida albicans. Fungal Genet Biol, 45, 221-231.

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

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

Odds, F.C., Bougnoux, M.E., Shaw, D.J., Bain, J.M., Davidson, A.D., Diogo, D., Jacobsen, M.D., Lecomte, M., Li, S.Y., Tavanti, A., Maiden, M.C., Gow, N.A., and d'Enfert, C. (2007). Molecular phylogenetics of Candida albicans. Eukaryotic Cell6, 1041-1052.

Braun, B.R., van Het Hoog, M., d'Enfert, C., Martchenko, M., Dungan, J., Kuo, A., Inglis, D.O., Uhl, M.A., Hogues, H., Berriman, M., Lorenz, M., Levitin, A., Oberholzer, U., Bachewich, C., Harcus, D., Marcil, A., Dignard, D., Iouk, T., Zito, R., Frangeul, L., Tekaia, F., Rutherford, K., Wang, E., Munro, C.A., Bates, S., Gow, N.A., Hoyer, L.L., Kohler, G., Morschhauser, J., Newport, G., Znaidi, S., Raymond, M., Turcotte, B., Sherlock, G., Costanzo, M., Ihmels, J., Berman, J., Sanglard, D., Agabian, N., Mitchell, A.P., Johnson, A.D., Whiteway, M., and Nantel, A. (2005) A human-curated annotation of the Candida albicans genome. PLoS Genet 1, 36-57.



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