Mode of action of metronidazole and a Bacteroides fragilis metA resistance gene in Escherichia coli.

The in-vivo mode of action of metronidazole and the MetA protein which confers resistance to metronidazole, was investigated in Escherichia coli wild type and DNA repair-deficient strains. All the E. coli strains were moderately susceptible to metronidazole under aerobic conditions but were more susceptible under anaerobic conditions, and the amount of DNA breakage was less under anaerobic than aerobic conditions. E. coli excision (uvr) and recombination (rec) mutants were more susceptible than DNA repair wild type strains. Metronidazole did not induce cell lysis in E. coli but caused single strand DNA breaks in wild type and repair-deficient E. coli strains. The MetA protein reduced DNA breakage caused by metronidazole in E. coli wild type and DNA repair-deficient strains grown under aerobic and anaerobic conditions, and inhibited the suppressor effect of the RecE protein in E. coli recBC strains. The MetA protein did not inactivate metronidazole.