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Abstract

Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate nutrient trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, I will discuss recent discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with zinc, a metal species which is essential nutrient in small quantities but is toxic in excess, and that M. tuberculosis has developed resistance mechanisms to zinc poisoning. I will also discuss recent findings regarding the role of two amino acid species, aspartate and asparagine, in nitrogen metabolism and mycobacterial physiology and virulence.
References:
Neyrolles O et al. 2015 Mycobacteria, metals, and the macrophage. Immunol Rev
Gouzy A et al. 2014 Nitrogen metabolism in Mycobacterium tuberculosis physiology and virulence. Nat Rev Microbiol
Gouzy A et al. 2014 Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress
during infection. PLoS Pathog
Gouzy A et al. Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate. Nat Chem Biol
Botella H et al. 2011 Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe

Bio

PhD (1994-1997) in microbiology in Luc Montagnier’s lab at Institut Pasteur, Paris, on microbial co-factors of the HIV virus

Postdoc in Douglas Young’s lab at Imperial College, London (1997-2000) on antigen presentation in Mtb-infected macrophages

Postdoc in Brigitte Gicquel’s lab at Institut Pasteur, Paris (2000-2004) on Mtb interactions with host cells

Appointed as research associate (2004) then research director (2009) at CNRS, Centre National de la Recherche Scientifique.

Head of the Mycobacterial Interactions with Host Cells group at Institute of Pharmacology & Structural Biology (IPBS), Toulouse, France.

Head of the TB & Infection biology department at IPBS.

 

CNRS Bronze medal (2009)

Prize from the Bettencourt-Schueller Foundation (2014)