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Mycobacterial evolution, physiology and virulence

Personnel involved

Principal investigators Claude Gutierrez, Yannick Poquet

Other personnel Florence Levillain, Yves-Marie Boudehen

Project outline

Most mycobacteria are environmental species, causing disease only occasionally when they encounter a susceptible human or animal host. A few species, such as Mycobacterium tuberculosis, have acquired the ability to parasitize host macrophages during the course of evolution and have become major pathogens. Recent genomic studies by our lab and others provided evidence that early episodes of horizontal transfer of genomic islands from surrounding environmental species likely contributed to the evolution of M. tuberculosis towards a sophisticated human-adapted pathogen. We are currently deciphering the function of several of these genomic islands, including toxin-antitoxin systems, in mycobacterial metabolism and pathogenicity.

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In addition to comparative genomics, we exploit global gene expression profiling of host cell and mycobacterial responses to infection. Dual host and pathogen DNA microarray analyses allowed to identify several families of eukaryotic and microbial genes whose expression is modulated upon infection. In particular, we recently identify a novel mechanism of innate immune control of pathogens through zinc intoxication, and resistance strategies in pathogenic mycobacteria involving P-ATPases were discovered. We are currently deciphering the molecular and cellular mechanisms involved in microbial poisoning by zinc in infected macrophages, and the function of several P-ATPases in M. tuberculosis physiology and virulence.

Collaborators

Priscille Brodin Centre d'Infection et d'Immunité de Lille Visit the Brodin lab webpage

Patrice Catty Laboratoire de Chimie et Biologie des Métaux, Grenoble Visit the Catty lab webpage

Marie-Ange Teste Genomics & Transcriptomics (GeT) Platform, Toulouse Take a look at the GeT activity

Axel Magalon Laboratoire de Chimie Bactérienne, Marseille Visit the Magalon lab webpage

Thierry Soldati University of Geneva, Switzerland Visit the Soldati lab webpage

Selected publications

Levillain, Poquet et al. 2017 Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation PLOS Pathog

Gouzy et al. 2014 Nitrogen metabolism in Mycobacterium tuberculosis physiology and virulence Nat Rev Microbiol

Gouzy et al. 2014 Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection PLOS Pathog

Gouzy et al. 2013 Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate Nat Chem Biol

Botella et al. 2011 Mycobacterial P1-type ATPases mediate resistance to zinc poisoning in human macrophages Cell Host Microbe

Jang et al. 2008 Horizontally acquired genomic islands in the tubercle bacilli Trends Microbiol

Becq et al. 2008 Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli Mol Biol Evol