Competition between H₄PteGlu and H₂PtePAS Confers para-Aminosalicylic Acid Resistance in Mycobacterium tuberculosis.

ABSTRACT: Tuberculosis remains a serious challenge to human health worldwide. para-Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by Mycobacterium tuberculosis (M. tuberculosis) dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene thyA caused PAS resistance in M. tuberculosis, but the mechanism is unclear. Here we showed that deleting thyA in M. tuberculosis resulted in increased content of tetrahydrofolate (H₄PteGlu) in bacterial cells as they rely on the other thymidylate synthase ThyX to synthesize thymidylate, which produces H₄PteGlu during the process. Subsequently

SUBMITTER: Yu JF 

PROVIDER: S-EPMC10812664 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature