De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation.

ABSTRACT: Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type Mtb evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ^-/-

SUBMITTER: Dwivedy A 

PROVIDER: S-EPMC7994828 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature