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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\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in cellulo<\/jats:italic>\n                    systems. We also discuss some of the recently emerged concepts regarding host adaptation to acid stress, with a special emphasis on central carbon metabolism. 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