Will defend his thesis entitled:

Transporteurs lipidiques dans la morphogenèse du champignon pathogène opportuniste de l’Homme, Candida albicans

Thesis supervisor: Martine Bassilana

Jury :

Président du jury
Dr. Robert Arkowitz, CNRS DR, iBV Université Côte d’Azur

Rapporteurs
Dr. Derek McCusker, CNRS DR, IBGC, Université de Bordeaux
Pr. James Konopka, Stony Brook University, NY, USA

Examinateurs
Dr. Cathy Jackson, CNRS DR, Inst. Jacques Monod, Paris
Dr. Guillaume Drin, CNRS DR, IPMC, Université Côte d’Azur

Abstract:
Candida albicans is a human opportunistic fungal pathogen that can cause superficial or systemic infections; its ability to change from an ovoid to a filamentous form is associated with its virulence. During this highly polarized filamentous growth, an accumulation of vesicles (Spitzenkörper), characteristic of filamentous fungi, as well as a polarized distribution of lipids, such as ergosterol, phosphorylated derivatives of phosphatidylinositol (PI(4)P, PI(4,5)P2) and phosphatidylserine (PS) is observed at the apex of filaments. However, the importance of the asymmetry of these lipids in the membrane bilayer is not completely understood. Flippases (P4-ATPases) transport lipids across the membrane bilayer to generate and maintain its asymmetry. C. albicans has 5 flippases, including Drs2 which is critical for filamentous growth and phosphatidylserine (PS) distribution. Furthermore, a drs2 deletion mutant is hypersensitive to fluconazole and copper. We show here that such a mutant is also critical to virulence in a mouse model of systemic infection. To clarify the role of Drs2 during C. albicans filamentous growth, we studied the distribution of this ATPase, as well as that of key lipids and regulators, during the initiation and maintenance of this growth process. We also characterized point mutants of Drs2, analogous to those altered for PS transport in S. cerevisiae. In addition, we examined the importance of other flippases, such as Dnf1-3, in invasive growth and the role of lipid transporters belonging to the oxysterol binding protein (Osh) family. Our results indicate in particular that Drs2 plays a unique role in the maintenance of invasive filamentous growth of C. albicans, which appears to be more critical after the first septum formation, and that an interaction between Drs2 and Osh4, via PI(4)P, plays an essential role during invasive filamentous growth.