Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin.
Enoxacin inhibits growth of Escherichia coli K12 strains primarily by binding to the GyrA subunit of DNA gyrase (topoisomerase II); strains with gyrA, but not gyrB, mutations are less susceptible to the bactericidal effects of this agent. In sensitive strains, enoxacin completely inhibits DNA synthesis within 5 min and produces drug-gyrase-DNA complexes at numerous sites throughout the E. coli chromosome, as shown by the formation of linear DNA molecules after detergent treatment. Enoxacin, even at subminimal inhibitory concentrations, induces the bacterial SOS system, even in partially resistant gyrA strains. This drug also inhibits the induced expression of the lacZ encoded beta-galactosidase, regardless of whether this gene is located on the chromosome, a low copy number F' plasmid or high copy number Col E1 related plasmids. This inhibition of gene expression at subminimal inhibitory concentrations is likely to be a factor, in addition to gyrase inhibition, in the elimination of Col E1 plasmids and to the reduction in R plasmid conjugal transfer. Enoxacin enhances the bactericidal effects of kanamycin in both in-vitro and in-vivo models, suggesting that this quinolone may be effective in the treatment of infections due to strains resistant to antibacterials as a consequence of plasmid encoded resistance determinants.
Courtright
J B
JB
Department of Biology, Marquette University, Milwaukee, WI 53233.
Turowski
D A
DA
Sonstein
S A
SA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002876:Chromosomes, Bacterial / Q000187:drug effects; D003227:Conjugation, Genetic / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000235:genetics; D004357:Drug Synergism; D004587:Electrophoresis, Agar Gel; D015365:Enoxacin; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005798:Genes, Bacterial / Q000187:drug effects*; D007612:Kanamycin / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology*; D011815:R Factors / Q000187:drug effects; D013014:SOS Response, Genetics / Q000187:drug effects; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D009287:Naphthyridines; D015365:Enoxacin; D007612:Kanamycin; D001616:beta-Galactosidase; D004250:DNA Topoisomerases, Type II