FEBS Lett. (2025) https://doi.org/10.1002/1873-3468.70023

Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms

Laudouze, J.; Canaan, S.; Gouzy, A.; Santucci, P.

Mycobacterium tuberculosis (Mtb) is a successful pathogen that has developed a variety of strategies to survive and replicate within host cells. Among them, resistance mechanisms that allow Mtb to cope with the acidic environment of the endolysosomal network play a crucial role in its host adaptation and pathogenesis. In this Review, we summarize our understanding regarding the molecular factors contributing to Mtb acid resistance and the maintenance of intrabacterial pH homeostasis within in vitro and in cellulo systems. We also discuss some of the recently emerged concepts regarding host adaptation to acid stress, with a special emphasis on central carbon metabolism. Finally, we introduce some of the current and future direction(s) in this fast-evolving field of research.