Acid Fasting: Modulation of Mycobacterium tuberculosis Metabolism at Acidic pH

Mycobacterium tuberculosis (Mtb) senses and adapts to acidic host environments during the course of pathogenesis. Mutants defective in acidic pH-dependent adaptations are often attenuated during macrophage or animal infections, supporting that these pathways are essential for pathogenesis and represent important new targets for drug discovery. This review examines a confluence of findings supporting that Mtb has restricted metabolism at acidic pH that results in the slowing of bacterial growth and changes in redox homeostasis. It is proposed that induction of the PhoPR regulon and anaplerotic metabolism, in concert with the restricted use of specific carbon sources, functions to counter reductive stress associated with acidic pH.