Slow growth ofMycobacterium tuberculosisat acidic pH is regulated byphoPRand host-associated carbon sources

摘要: During pathogenesis, Mycobacterium tuberculosis (Mtb) colonizes environments, such as the macrophage or necrotic granuloma, that are acidic and rich in cholesterol fatty acids. The goal of this study was to examine how pH available carbon sources interact regulate Mtb physiology. Here we report growth at requires host-associated function intersection glycolysis TCA cycle, pyruvate, acetate, oxaloacetate cholesterol. In contrast, other tested sources, fully arrests its establishes a state non-replicating persistence. Growth-arrested is resuscitated by addition pyruvate suggesting arrest due pH-dependent checkpoint on metabolism. Additionally, demonstrate phoPR two-component regulatory system required slow functions maintain redox homeostasis. Transcriptional profiling functional metabolic studies signals from source integrated remodel pathways associated with anaplerotic central metabolism, lipid anabolism regeneration oxidized cofactors. Because for virulence animals, suggest pH-driven adaptation may be critical pathogenesis.