Séminaire CIRI (06.07.2023) : Dr. Olivier Neyrolles

Olivier Neyrolles, Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse CNRS, UPS, Toulouse, "Decoding the battle between Mycobacterium tuberculosis and host metal defenses"

Abstract: The design of new drugs to combat tuberculosis requires a better understanding of the mechanisms by which the tuberculosis bacillus, Mycobacterium tuberculosis, survives and grows within the cells and tissues of its host. Our laboratory is interested in deciphering the close links between the evolution, physiology and virulence of the TB bacillus. Here I will present our recent work, based on targeted and genome-wide approaches, aimed at deciphering the strategies used by M. tuberculosis to counter nutritional immunity, in particular host-mediated metal intoxication in the mycobacterial vacuole, a novel mechanism of innate immunity. In particular, we and others have discovered that, in addition to their well-known ability to limit the access of intracellular pathogens to essential elements such as iron, macrophages can accumulate transition metals, notably zinc and copper, in the phagocytosis vacuole, at concentrations potentially toxic to microorganisms. To resist this stress, we have identified metal efflux pumps of the P-ATPase superfamily in the tuberculosis bacillus, as well as a new type of small metallochaperone capable of binding metals and stabilizing the efflux pumps in dynamic membrane platforms whose exact structure remains to be elucidated. These results open perspectives for the development of new treatments and for the understanding of the metallobiology of host-pathogen interactions and bacteria in general.