Growth ofMycobacterium tuberculosisat acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity

• DOI: 10.1073/pnas.2024571118
• Publication Date: 2021-08-02T20:36:57Z
• Authors: Alexandre Gouzy; Claire Healy; Katherine A. Black; Kyu Y. Rhee; Sabine Ehrt
• Keywords: Glycerol; 0301 basic medicine; Carbon Isotopes; Gluconeogenesis; Glyceraldehyde-3-Phosphate Dehydrogenases; Mycobacterium tuberculosis; Hydrogen-Ion Concentration; Lipid Metabolism; Isocitrate Lyase; Carbon; 3. Good health; 03 medical and health sciences; Glucose; Bacterial Proteins; Host-Pathogen Interactions; Reactive Oxygen Species; Phosphoenolpyruvate Carboxykinase (ATP); Oleic Acid

SignificanceTuberculosis (TB) remains a global health concern despite the availability of antibiotics to treat this disease. Understanding the metabolic state of the bacteria during infection is crucial to identifying novel drug targets that are vital toMycobacterium tuberculosissurvival. Here, we demonstrate thatM. tuberculosiscentral carbon metabolism is altered in response to acidic pH, a host-imposed stress, causing the pathogen to depend on lipids for growth. Continuous fatty acid supplementation at acidic pH is a simple and effective approach to investigateM. tuberculosisin a metabolic state that more closely reflects that of bacteria during infection and might facilitate the identification of anti-TB drugs with a greater likelihood to be active in vivo.