Nitrate-responsive Mycobacterial Intracytoplasmic Membranes dampen Inflammation during Mycobacterium tuberculosis Infection
Keck, C.; Tachon, S.; Sayes, F.; Musiani, D.; Gianetto, Q. G.; Matondo, M.; Vos, M.; Brosch, R.; Enninga, J.
Show abstract
Subcellular compartmentalization of metabolic processes is a main feature of prokaryotic and eukaryotic architecture. Environmental bacteria generate intracytoplasmic membranes (ICMs) as a crucial strategy to adapt their metabolism to environmental changes. While pathogenic intracellular bacteria also perceive various stressful stimuli during host interactions, the subsequent re-organization of their internal architecture has not been explored. Using cryo-electron tomography, we show that Mycobacterium tuberculosis (Mtb), a major human pathogen, is able to form ICMs outside and inside host cells in a strain-dependent manner. We characterize these Mycobacterial intracytoplasmic Membranes (MIMs) as nitrate-induced structures involved in regulation of metabolism. Furthermore, we uncover that MIM formation during macrophage infection correlates with the ability of Mtb to dampen cellular inflammatory responses. Our findings reveal a previously uncharacterized cytoplasmic structure in Mtb and link it to a functional mechanism that enables the bacterium to adapt to its intracellular niche.
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