Research directions
Virulence factors in pathogenic fungi
Candida albicans is an opportunistic pathogen causing oral, vaginal or systemic infections in immuno-compromized patients. Such patients, like HIV+, transplanted patients and those receiving chemotherapy, are in constant augmentation. In up to 30% of the patients with C. albicans systemic infections, the issue is fatal. Control of C. albicans infections is essentially achieved using treatments inhibiting microbial growth, such as treatment with azoles. For HIV+ and transplanted patients, long-time prophylactic and therapeutic antifungal treatment are needed. C. albicans exposed for a long time to these antifungals adapts to this stress, and develops resistance leading to treatment failure. Therefore, alternative treatment strategies are needed.
Host-pathogen interaction is a key component of any infectious process. Treatment modifying this relationship can be designed. Transcription factors (TF) are potentially important for C. albicans virulence since they integrate several signals from host environment and participate in an adapted microbial response.
In this project, we develop an original approach to analyze a collection of C. albicans transcription factor mutant strains in vivo. A collection of TF mutant strains are screened in a mice model of systemic infection in order to identify those factors crucial for virulence. Additional analysis is performed on the selected TF to understand at which steps of the infection they are involved and which element of the host defense they target.
Genes under the control of those TF will then be identified in order to determine which metabolic pathways of the fungus are involved in the infection.
This analysis is important for C. albicans infection but will constitute a model for other pathogenic fungi. A mid-term outcome of this project will be a better understanding of the global host-fungus interactions, which may lead to the development of new drugs and treatment
