Broken beyond repair: TA system ParE toxins mediate effective gyrase inhibition without driving resistance.

ABSTRACT: DNA gyrase is an essential bacterial-specific type IIA topoisomerase that corrects DNA overwinding during transcription and replication. Compounds capable of stabilizing gyrase-mediated double-strand DNA breaks are valuable antibacterials; however, these can trigger error-prone repair, potentially inducing DNA mutations leading to antimicrobial resistance. ParE toxin proteins, which belong to a family of type II toxin-antitoxin systems, inhibit DNA gyrase and promote the persistence of double-strand DNA breaks. However, it is unclear if the ParE-induced gyrase inhibition is equivalent for all ParE family members, or if any mutations arise and can accumulate to cause antibiotic resistance. Selected chromosomal ParE toxins were examined for toxicity to their native bacterial hosts, and the f

SUBMITTER: Tu C-H 

PROVIDER: S-EPMC11925232 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature