title: Novobiocin Susceptibility of MukBEF-Deficient Escherichia coli Is Combinatorial with Efflux and Resides in DNA Topoisomerases.
abstract: Condensins play a key role in the global organization of bacterial chromosomes. In Escherichia coli, the inactivation of its sole condensin MukBEF induces severe growth defects and renders cells hypersusceptible to novobiocin. We report here that this hypersusceptibility can be observed in TolC-deficient cells and is therefore unrelated to multidrug efflux. We further show that mutations in MukE that impair its focal subcellular localization potentiate novobiocin and that the extent of the potentiation correlates with the residual activity of MukE. Finally, both DNA gyrase and topoisomerase IV might partially complement novobiocin susceptibility in a temperature-dependent manner. These data indicate that the observed antibiotic susceptibility resides in both type II DNA topoisomerases and is efflux independent. Furthermore, novobiocin susceptibility is associated with the activity of MukBEF and can be induced by its partial inactivation, which makes the protein a plausible target for inhibition.
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Zoya M
authors.initials: ZM
authors.lastname: Petrushenko
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Helen I
authors.initials: HI
authors.lastname: Zgurskaya
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA valya@ou.edu.
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Rybenkov
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000378:metabolism; D026942:DNA Topoisomerases / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism; D009675:Novobiocin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D009675:Novobiocin; D027101:DNA Topoisomerase IV; D026942:DNA Topoisomerases; D027081:DNA Gyrase