Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Fungal Biology and Pathogenicity Unit – INRA USC2019
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
C. albicans is currently the main fungal pathogen of humans. While a commensal of the gastro-intestinal and genital tracts, it is responsible for superficial infections in healthy individuals and systemic infections in patients with a debilitated immune system. Despite the availability of antifungals, mortality rates associated to invasive candidiasis remain high (30-50%). The Fungal Biology and Pathogenicity Unit is using post-genomic and genetic approaches in order to investigate several aspects of the biology of Candida albicans. Genome dynamics in this obligate diploid species is studied with the aim to assess its contribution to the success of C. albicans as a commensal or pathogen. We are also investigating the molecular mechanisms that underlie biofilm formation with the specific aim to understand how these microbial communities achieve an intrinsic tolerance to most antifungals. Finally, we use genetic approaches to decipher the signaling networks regulating C. albicans morphogenesis, a process key to pathogenesis and biofilm formation.
Contribution to the programme
The Fungal Biology and Pathogenicty Unit will contribute to IBEID by investigating the molecular mechanisms that C. albicans has established to control the dynamics of its genome, the yeast-to-hypha switch, the formation of biofilms on abiotic surfaces as well as the colonization and invasion of epithelia. In particular, we will explore the mechanisms that regulate loss-of-heterozygosity in C. albicans and explore to what extent this process impacts C. albicans fitness during commensalism and disease. Studies on morphogenesis will aim to decipher the regulatory networks that control hyphal differentiation and, possibly, identify novel targets for the development of antifungal strategies. The study of biofilm formation, currently focused on the colonization of biotic surfaces, will be extended to the colonization of the gastro-intestinal tract and its invasion in order to elucidate the mechanisms that underlie the transition from commensalism to pathogenesis. These projects will use multidisciplinary approaches combining genetics, post-genomics, imaging and in vitro and in vivo models.
References over the past 5 years
1. Gutierrez-Escribano, P., U. Zeidler, M. B. Suarez, S. Bachellier-Bassi, A. Clemente-Blanco, J. Bonhomme, C. R. Vazquez de Aldana, C. d'Enfert, and J. Correa-Bordes. 2012. The NDR/LATS Kinase Cbk1 Controls the Activity of the Transcriptional Regulator Bcr1 during Biofilm Formation in Candida albicans. PLoS Pathog 8:e1002683.
2. Bonhomme, J., M. Chauvel, S. Goyard, P. Roux, T. Rossignol, and C. d'Enfert. 2011. Contribution of the glycolytic flux and hypoxia adaptation to efficient biofilm formation by Candida albicans. Mol Microbiol 80:995-1013.
3. Vediyappan, G., T. Rossignol, and C. d'Enfert. 2010. Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to beta-glucans. Antimicrob Agents Chemother 54:2096-2111.
4. Moreno-Ruiz, E., M. Galan-Diez, W. Zhu, E. Fernandez-Ruiz, C. d'Enfert, S. G. Filler, P. Cossart, and E. Veiga. 2009. Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11:1179-1189.
5. Enjalbert, B., A. Rachini, G. Vediyappan, D. Pietrella, R. Spaccapelo, A. Vecchiarelli, A. J. Brown, and C. d'Enfert. 2009. A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections. Infect Immun 77:4847-4858.
6. Diogo, D., C. Bouchier, C. d'Enfert, and M. E. Bougnoux. 2009. Loss of heterozygosity in commensal isolates of the asexual diploid yeast Candida albicans. Fungal Genet Biol 46:159-168.
7. 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, and 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.