Clinically Relevant Mutations of Mycobacterial GatCAB Inform Regulation of Translational Fidelity.

ABSTRACT: Most bacteria employ a two-step indirect tRNA aminoacylation pathway for the synthesis of aminoacylated tRNA^Gln and tRNA^Asn. The heterotrimeric enzyme GatCAB performs a critical amidotransferase reaction in the second step of this pathway. We have previously demonstrated in mycobacteria that this two-step pathway is error prone and translational errors contribute to adaptive phenotypes such as antibiotic tolerance. Furthermore, we identified clinical isolates of the globally important pathogen Mycobacterium tuberculosis with partial loss-of-function mutations in gatA, and demonstrated that these mutations result in high, specific rates of translational error and increased rifampin tolerance. However, the mechanisms by which these clinically derived mutations in

SUBMITTER: Li YY 

PROVIDER: S-EPMC8406222 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature