Figure 3.

Mtb metabolism for survival and antibiotic defense in host cells. The Mtb survival strategy using host metabolism is shown as a red line. Mtb preferentially utilizes host pyruvate for intracellular proliferation. Similarly, lactate produced by glycolysis in the host is used for pathogens. Mtb Rv2498c decomposes itaconate to produce AcCoA and pyruvate, and leucine decomposes to produce AcCoA and acetoacetate, which are used as a nutrient source for Mtb. Lipid bodies in macrophages mainly consist of triacylglycerol (TAG) and cholesterol esters (CE) and can be a source of nutrients and components for Mtb. Inhibition of Mtb growth is shown as a blue line. Itaconate, a macrophage metabolite produced during the inflammatory response of Mtb-infected hosts, inhibits bacterial isocitrate lyse (ICL), a key enzyme in the glyoxylate cycle of mycobacteria. Antibiotic-resistant bacteria inhibit metabolism in antiseptic antibiotic treatment, but antibiotic susceptibility can be improved by using metabolic adjuvants to activate central carbon metabolism. Antibiotic resistance from altered Mtb metabolism and metabolism-related genes are shown as purple lines. Mutations in the glpk coding sequence reduce antibiotic efficacy and contribute to a drug-tolerant phenotype. PrpR mutations alter propionyl-CoA metabolism, resulting in attenuated antibiotic efficacy and induced multiple drug resistance. The Mtb killing effect is enhanced by an enzyme encoded with Ppt hydrolase (pptH) that hydrolyzes phosphopantetheinyl transferase (PptT) present in the CoA pathway. However, rv2795c loss-of-function mutations in Mtb confer resistance to antibiotics.