Molecular Mycology - CNRS FRE2849  


  HEADDr DROMER Françoise / dromer@pasteur.fr
  MEMBERSProf. BRETAGNE Stéphane / Dr CHARLIER Caroline / Dr DANNAOUI Eric / DESNOS-OLLIVIER Marie
Dr FSIHI Hafida / Prof. GANTIER Jean-Charles / GARCIA-HERMOSO Dea / Dr JANBON Guilhem
LEE Nancy / Prof. LORTHOLARY Olivier / Dr MEMET Sylvie / RIERA-BONET Marta / SCHWARZ Patrick


  Annual Report

A better understanding of the interactions between the hosts and pathogenic fungi should improve the prognosis of systemic fungal infections. Our projects focus on Cryptococcus neoformans and Candida albicans's pathogenicity by studying the host (clinical and epidemiological studies, animal models of infection) and the fungus (virulence factors, variability) sides. There is an efficient interplay between research and expertise at the National Reference Center for Mycoses and Antifungals.

Cryptococcus neoformans

Cryptococcosis is a life-threatening disseminated meningoencephalitis that occurs in up to 30% of patients with AIDS in tropical areas in Africa and South East Asia. C. neoformans is surrounded by a capsule made of polysaccharides, which is a major virulence factor.

C. neoformans capsule (G. Janbon): Our hypothesis is that in addition to its presence, the variability of the capsule structure should play a role in the yeast's virulence. Genes coding for proteins involved in the biosynthetic pathways of the capsule have been cloned and are studied for their involvement in the pathophysiology of the infection and for more basic projects (regulation of the nucleotide-sugars transport in the vesicles, relationship between the splicing of some specific genes and the capsule structure…).

C. neoformans crossing of the blood brain barrier (BBB) (F. Dromer): Little is known on the mechanisms allowing C. neoformans to cross the BBB. In collaboration with F. Chrétien (INSERM EMI 0011, Hôpital H. Mondor, Créteil) we are analyzing the mechanisms allowing C. neoformans crossing of the BBB. We are currently using various models/techniques to study the interactions between C. neoformans and monocytes.

Host response to CNS infection by C. neoformans (S. Mémet): Very few data are available as regards to the role of host cells, namely endothelial and glial cells, in crossing of the BBB, dissemination of C. neoformans, as well as in induction/repression of an inflammatory response. We have therefore initiated a thorough analysis of the inflammatory signaling triggered by C. neoformans, with particular emphasis on the role of the transcription factor NF-κB, a major regulator of inflammation, innate and acquired immunity. Experiments are being conducted with two yeasts that induce either a scanty (C. neoformans) or a very strong (C. albicans) inflammatory response. Preliminary results with a human BBB endothelial cell model indicate that although both fungi activate NF-κB in these cells, the time-course of activation is different.

Candida

Candida albicans is a commensal of the digestive tract responsible for a wide range of infections in immunocompetent and immunodeficient patients.

Biofilm formation in C. albicans and Candida glabrata (G. Janbon)

Biofilms are tridimensional structures composed of microorganisms that developed on various surfaces. Our objective in collaboration with 4 units of the campus is to determine molecular events leading to the development of biofilms (PTR173). We have demonstrated that an adhesin encoding gene was regulated by the sub-telomeric silencing machinery, a signal activated during biofilm growth and the Yak1p kinase. Our ongoing program is the study of this important kinase.

National Reference Center Mycoses and Antifungals NRCMA, F. Dromer, O. Lortholary): Our missions include (1) expertise in the identification of pathogenic fungi and their molecular typing, as well as antifungal susceptibility testing and advice for the management of patients with severe mycoses; (2) epidemiological survey of all rare, severe or exotic mycoses as well as the emergence of resistance to antifungal drugs, with notification through a secured website RESOMYC. Our recent studies include:

- Analysis of determinants of clinical presentation and short-term and long-term outcome during cryptococcosis in patients with AIDS

- Demonstration of a lack of correlation between in vitro results of antifungal susceptibility determination and early outcome during cryptococcosis

- Demonstration that resistance of C. neoformans isolates to flucytosine in vitro does not prevent synergy with amphotericin B in vitro and in vivo

- Design of molecular tools for the identification of agents of black grains mycetoma and of zygomycetes.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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