Phenotype-Guided Comparative Genomics Identifies the Complete Transport Pathway of the Antimicrobial Lasso Peptide Ubonodin in Burkholderia.

ABSTRACT: New antibiotics are needed as bacterial infections continue to be a leading cause of death, but efforts to develop compounds with promising antibacterial activity are hindered by a poor understanding of─and limited strategies for elucidating─their modes of action. We recently discovered a novel lasso peptide, ubonodin, that is active against opportunistic human lung pathogens from the Burkholderia cepacia complex (Bcc). Ubonodin inhibits RNA polymerase, but only select strains were susceptible, indicating that having a conserved cellular target does not guarantee activity. Given the cytoplasmic target, we hypothesized that cellular uptake of ubonodin determines susceptibility. Although Bcc strains harbor numerous nutrient uptake systems, these organisms lack close homologues of the

SUBMITTER: Do T 

PROVIDER: S-EPMC9454059 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature