Inhibition of Fatty Acid Oxidation Promotes Macrophage Control of Mycobacterium tuberculosis

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Abstract
Mycobacterium tuberculosis (Mtb) is the leading infectious disease killer worldwide. We discovered that intracellular Mtb fails to grow in macrophages in which fatty acid β-oxidation (FAO) is blocked. Macrophages treated with FAO inhibitors rapidly generate a burst of mitochondria-derived reactive oxygen species, which promotes NADPH oxidase recruitment and autophagy to limit the growth of Mtb. Furthermore, we demonstrate the ability of trimetazidine to reduce pathogen burden in mice infected with Mtb. These studies will add to the knowledge of how host metabolism modulates Mtb infection outcomes.
Funding Information
  • Center for Drug Discovery, Pfeiffer Foundation Drug Discovery Fund, Washington University (LEAP)
  • Potts Memorial Foundation (N/A)
  • HHS | National Institutes of Health (AI128427, AI130454)
  • HHS | National Institutes of Health (DK11003404)
  • HHS | National Institutes of Health (R35 HL135799)

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