The effect of mutations in the SOS response on the kinetics of quinolone killing.
The SOS response is induced in Escherichia coli by agents that damage DNA, such as quinolone antibiotics. It has been proposed that induction of the SOS response by these agents may have a role in the mechanism of quinolone action. SOS mutants derived from Escherichia coli AB1157 were investigated by susceptibility testing and killing kinetic studies at various quinolone concentrations to determine whether SOS response induction was protective or damaging to quinolone-treated bacteria. Susceptibility testing showed some differences between the SOS mutants, but killing kinetic studies demonstrated further differences, some of which could be explained with respect to the SOS phenotype. The effect of ciprofloxacin and nalidixic acid on the mutants cannot be explained with respect to the SOS phenotype, although the presence of a defective SOS response makes the bacteria less sensitive to the action of these agents. Evidence is provided that the induction of the SOS response may be protective to fleroxacin and enoxacin treated bacteria. These results suggest that quinolones may not have a common mechanism of action, as was first thought.
Walters
R N
RN
Department of Medical Microbiology, Medical School, University of Birmingham, UK.
Piddock
L J
LJ
Wise
R
R
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D005798:Genes, Bacterial / Q000187:drug effects; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013014:SOS Response, Genetics / Q000187:drug effects*
D042462:4-Quinolones; D000890:Anti-Infective Agents