Specificity determinants for autoproteolysis of LexA, a key regulator of bacterial SOS mutagenesis.

ABSTRACT: Bacteria utilize the tightly regulated stress response (SOS) pathway to respond to a variety of genotoxic agents, including antimicrobials. Activation of the SOS response is regulated by a key repressor-protease, LexA, which undergoes autoproteolysis in the setting of stress, resulting in derepression of SOS genes. Remarkably, genetic inactivation of LexA's self-cleavage activity significantly decreases acquired antibiotic resistance in infection models and renders bacteria hypersensitive to traditional antibiotics, suggesting that a mechanistic study of LexA could help inform its viability as a novel target for combating acquired drug resistance. Despite structural insights into LexA, a detailed knowledge of the enzyme's protease specificity is lacking. Here, we employ saturation and posi

SUBMITTER: Mo CY 

PROVIDER: S-EPMC4030785 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature