Disrupting Transcription and Folate Biosynthesis Leads to Synergistic Suppression of Escherichia coli Growth.

ABSTRACT: The use of synergistic antibiotic combinations has emerged as a viable approach to contain the rapid spread of antibiotic-resistant pathogens. Here we report the discovery of a new strongly synergistic pair - microcin J25 and sulfamonomethoxine. The former is a lasso peptide that inhibits the function of RNA polymerase and the latter is a sulfonamide antibacterial agent that disrupts the folate pathway. Key to our discovery was a screening strategy that focuses on an antibiotic (microcin J25) that targets a hub (transcription) in the densely interconnected network of cellular pathways. The rationale was that disrupting such a hub likely weakens the entire network, generating weak links that potentiate the growth inhibitory effect of other antibiotics. We found that MccJ25 potentiates five

SUBMITTER: Chen PH 

PROVIDER: S-EPMC9314896 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature