Molecular Mycology - CNRS URA3012  


  HEADDr DROMER Françoise / dromer@pasteur.fr
  MEMBERSDr ALANIO Alexandre, ANFRY Lucile, BEN ABDALLAH Mariem, Dr BOUKRIS-SITBON Karine, BOUYSSIE Reine, Pr BRETAGNE Stéphane, Dr DANNAOUI Eric, DESNOS-OLLIVIER Marie, Pr GANTIER Jean-Charles, Dr GARCIA-HERMOSO Dea, HOINARD Damien, Pr LORTHOLARY Olivier, Dr MEMET Sylvie, RAOUX-BARBOT Dorothée, STURNY-LECLERE Aude, TOURNAIRE Marc, Frédérique VERNEL-PAUILLAC


  Annual Report

Invasive mycoses represent an important burden in terms of morbidity and mortality. Studying the infection processes contributes to the understanding of the causative agent’s biology and can potentially lead to improved patients’ management. In the field of medical mycology, many aspects of the pathogenic fungi biology and of their interactions with their human or animal hosts are yet to discover. The Molecular Mycology unit includes the French National Reference Center for Mycoses and Antifungals (NRCMA). The clinical isolates and epidemiological data that we collect provide a means to assess the medical relevance of our experimental findings.

Our projects are focused on cryptococcosis. Cryptococcosis is a life-threatening disseminated meningoencephalitis that occurs in patients with AIDS. The recent estimation by the Center for Diseases Control suggests nearly 1 million of cases/year worldwide associated with more than 600,000 annual deaths. Our studies combine analysis of the host (clinical and epidemiological studies, animal and cellular models) and the yeast (diversity, variability, virulence) sides.

C. neoformans diversity during infection in France (M Desnos-Ollivier, D. Raoux, F. Dromer): C. neoformansis a haploid yeast with a bipolar mating system (asexual multiplication + sexual reproduction giving rise to haploids, diploids and hybrids). It exists in 2 varieties neoformans(serotype D) and grubii(serotype A). French clinical isolates of C. neoformans var. neoformans and var. grubiirecovered during the prospective multicenter CryptoA/D study are currently analyzed to determine whether some molecular types are responsible for more severe infections. We recently uncovered using molecular analysis of unpurified isolates, that mixed infections in patients with cryptococcosis are more common than previously thought. Thus, the concept of one strain/one infection does not hold true for C. neoformansand may apply to other environmentally-acquired fungal pathogens. Furthermore, the possibility of mixed and/or evolving infections should be taken into account when developing preventive and therapeutic strategies against these pathogens.

Biomarkers of prognosis during cryptococcosis (F. Vernel-Pauillac, A. Sturny-Leclère, A. Alanio, F. Dromer): Fungal determinants and/or host factors are probably involved in the diversity of clinical presentation and outcome of cryptococcosis. We are using well-characterized clinical isolates of C. neoformans, cellular and animal models of infection to uncover potential markers of prognosis (antibodies, mediators profiles, fungal determinants) during infection.

Host response to C. neoformansinfection(S. Mémet): A lot remained to be deciphered as regards the response of host cells to C. neoformansinfection, and their role in the induction/repression of an inflammatory response. We have initiated a thorough analysis of the inflammatory signalling triggered by C. neoformans, with particular emphasis on the role of the transcription factor NF-κB, a key regulator of inflammation, innate and acquired immunity. Experiments conducted on macrophages in vitro and in vivo with κB-reporter mice revealed that this fungus activates NF-κB with a specific time-course and that such activation affects the survival and growth of macrophages.

National Reference Center for Mycoses and Antifungals (F. Dromer, O. Lortholary): Our missions include (1) expertise in the identification and characterization of pathogenic fungi and advice for the management of patients with severe mycoses; (2) epidemiological survey of all rare, severe or imported mycoses as well as of the emergence of resistance to antifungal drugs, with notification through a secured website RESOMYC; (3) design of new typing systems (4) phylogenetic studies. By the systematic polyphasic identification of all isolates collected at the NRCMA, we uncovered new cryptic species among Lichteimiaspp. and Sacksenaeaspp., responsible for severe mucormycoses, and contributed to the diagnosis of several invasive fungal infections due to emerging filamentous fungi or yeasts.

Keywords: Cryptococcus neoformans, co-infections, antibodies, NFKappa B, epidemiology, cryptococcosis, mucormycoses

dromer.jpg

Figure:intracellular proliferation of calcofluor-labelled C. neoformansinside murine macrophages (J774 cells)



  Publications

Alvarez E, Garcia-Hermoso D, Sutton DA, Cano JF, Stchigel AM, Hoinard D, Fothergill AW, Rinaldi MG, Dromer F, Guarro J. Molecular phylogeny and proposal of two new species of the emerging pathogenic fungus Saksenaea.J Clin Microbiol. 2010;48(12):4410-6.PMID: 20926710

Desnos-Ollivier M, Patel S, Spaulding AR, Charlier C, Garcia-Hermoso D, Nielsen K, Dromer F. Mixed Infections and In Vivo Evolution in the Human Fungal Pathogen Cryptococcus neoformans. mBio. 2010;1(1)PMID: 20689742

Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291-322.PMID: 20047480

Raymond B, Ravaux L, Mémet S, Wu Y,Sturny-Leclère A, Leduc D, Denoyelle C, Goossens PL, Payá M, Raymondjean M, Touqui L. Anthrax lethal toxin down-regulates type-IIA secreted phospholipase A(2) expression through MAPK/NF-kappaB inactivation. Biochem Pharmacol. 2010 Apr 15;79(8):1149-55.PMID: 19962969

Scott-Algara D, Balabanian K, Chakrabarti LA, Mouthon L, Dromer F, Didier C, Arenzana-Seisdedos F, Lortholary O. Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4. Blood. 2010;115(18):3708-17.PMID: 20038787





Activity Reports 2010 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr