Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance.

ABSTRACT:

Unlabelled

Bacterial DNA is maintained in a supercoiled state controlled by the action of topoisomerases. Alterations in supercoiling affect fundamental cellular processes, including transcription. Here, we show that substitution at position 87 of GyrA of Salmonella influences sensitivity to antibiotics, including nonquinolone drugs, alters global supercoiling, and results in an altered transcriptome with increased expression of stress response pathways. Decreased susceptibility to multiple antibiotics seen with a GyrA Asp87Gly mutant was not a result of increased efflux activity or reduced reactive-oxygen production. These data show that a frequently observed and clinically relevant substitution within GyrA results in altered expression of numerous genes, including those important

SUBMITTER: Webber MA 

PROVIDER: S-EPMC3735185 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature