Project #7143
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#7143 : Modeling mitochondrial metabolism dormant Cryptococcus neoformans
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Name of Applicant : Benjamin Hommel
Date of application : 29-09-2016
Unit : Molecular Mycology
Location : Duclaux-RDCH-22
Phone : 3255
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Project context and summary :

Cryptococcus neoformans is a ubiquitous yeast present in the environment that is able to interact closely with numerous organisms including amoeba, paramecium or nematodes. The interaction with these organisms shaped its virulence with acquisition of infectious properties as a consequence especially in mammals . The ability to survive nutrient starvation, oxidative stress, desiccation, both in the environment and during infection, indicates a high level of physiological and metabolic plasticity of the yeast. In humans, after primary infection during childhood, the yeast is able to survive within the host for years before reactivation upon immunosuppression, leading to a life threatening  disseminated fungal infection. This phenomenon, called dormancy / quiescence is one of the main biological features of this fungus in relation with disease's pathogenesis. It is well known in bacteria (tuberculosis), parasites (Plasmodium, Toxoplasma). In C. neoformans, dormancy has only been demonstrated epidemiologically in our laboratory but not experimentally so far. We developed an assay where yeasts cells exhibiting characteristics of potentially dormant cells were generated. Indeed, dormant cells are characterized by a low metabolic activity sometimes undetectable under normal laboratory conditions, altered growth capacity, and the ability to resuscitate upon adequate stimulus. Dormant cells are known to have increased mitochondrial masse and activity justifying a screening strategy of a collection of KO mutants for mitochondrial proteins. In parallel the whole proteome, transcriptome and secretome will be obtain with the ambition to correlate these parameters. Our current project aims at exploring the metabolism of the dormant yeast to have a comprehensive picture of the pathways that are required for the maintenance of dormancy and fo exit from dormancy.  

Related team publications :
Epidemiological evidence for dormant Cryptococcus neoformans infection, JCM, 1999, Garcia-Hermoso D, Janbon G, Dromer F
Cryptococcus neoformans host adaptation: toward biological evidence of dormancy, mBio 2015, Alanio A, Vernel-Pauillac F, Sturny-Leclère A, Dromer F
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Status : Closed

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