Bactericidal activities of five quinolones for Escherichia coli strains with mutations in genes encoding the SOS response or cell division.
The bactericidal effects of five quinolones (at the optimum bactericidal concentration for strain AB1157) on 15 strains of Escherichia coli with mutations in genes for the SOS response or cell division was studied by a viable-count method. The kill rate data were normalized for growth rate and compared to those for the wild type, AB1157. Similar MICs of enoxacin and fleroxacin were obtained for all mutants; however, different mutants had differing susceptibilities to ciprofloxacin, norfloxacin, and nalidixic acid. Killing kinetic studies showed that mutants with constitutive RecA expression (recA730 and spr-55 mutants) survived longer than AB1157 with all quinolones. Mutants deficient in SOS induction, e.g., recA430 and lexA3 mutants, also survived longer, suggesting that induction of the SOS response by quinolones is harmful to wild-type cells. Recombination repair-deficient mutants (recB21, recC22, and recD1009 mutants) were killed more rapidly than AB1157, as were excision repair mutants, except with nalidixic acid. Mutants which were unable to filament (sfiA11 and sfiB114 mutants) survived longer than AB1157 with all agents, but a mutant defective in the Lon protease was killed more quickly. It was concluded that (i) recombination and excision repair were involved in the repair of quinolone-damaged DNA and (ii) continuous induction (in response to exposure to quinolones) of the SOS response, and hence induction of the cell division inhibitor SfiA, causes cell filamentation and thereby contributes to the bactericidal activity of quinolones.
Piddock
L J
LJ
Department of Medical Microbiology, Medical School, University of Birmingham, Edgbaston, United Kingdom.
Walters
R N
RN
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002455:Cell Division; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013014:SOS Response, Genetics / Q000187:drug effects*
D042462:4-Quinolones; D000890:Anti-Infective Agents