ACA kills Mycobacterium tuberculosis and M. bovis by targeting cell wall core assembling protein CpsA.

ABSTRACT: Tuberculosis (TB), caused by Mycobacterium tuberculosis, still globally threatens human health. With the emergence of multidrug-resistant strains, there is an imperative need to discover new anti-TB agents and identify novel drug targets. Here, we report that the compound ACA, namely 3-azidothiophene-2-carboxylic acid, can kill M. tuberculosis by targeting the bacterial cell wall core assembling process. Whole-genome sequencing of spontaneous ACA-resistant mutants identified single-nucleotide variants in the cpsA2 ligase gene responsible for the covalent attachment of arabinogalactan and peptidoglycan. The cell wall of cpsA2 or its homolog cpsA1-deleted mutant H37Ra strains show increased permeability and drug sensitivity, which is similar to the ACA-treated mycobacteria. Both cpsA1 and cp

SUBMITTER: Huang F 

PROVIDER: S-EPMC12658130 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature