Combined lactate- and phosphate-dependent cytoplasmic acidification is associated with Mycobacterium tuberculosis growth arrest at acidic pH.

Depletion of phosphate restores Mycobacterium tuberculosis growth on lactate at acidic pH by preventing cytoplasmic acidification and proton motive force stress.

• Why it matters: Understanding how M. tuberculosis responds to acidic environments and specific carbon sources is crucial for developing strategies to combat persistent infections, as acid growth arrest may contribute to bacterial survival.
• What they did: The study used transposon mutants and transcriptional profiling to investigate the mechanisms behind acid growth arrest, focusing on mutants in phosphate transporter genes and the role of regX3 in lactate metabolism at low pH.
• The result: Findings show that lactate- and phosphate-dependent cytoplasmic acidification is linked to PMF stress and growth arrest, with low phosphate activating regX3, which may modify cell-envelope pathways to enable growth on lactate at acidic pH.