Chromosomal Breakage in the B. fragilis Group Induced by Metronidazole Treatment

Metronidazole is used in clinical practice for the treatment of protozoan and anaerobic infections. Under anaerobic conditions, 5-nitroimidazoles are reduced to cytotoxic nitroradicals which have been shown to act by non-specific binding to, and inactivation of the organism's DNA and enzymes. Among anaerobes, the Bacteroides fragilis group is the most relevant both in terms of frequency of isolation and antimicrobial resistance. In the present study we investigated the mechanism of action of metronidazole in the B. fragilis group. We evaluated chromosomal DNA integrity in susceptible and resistant strains during a period of 5 h after metronidazole exposure and we quantified the drug remaining in the medium after microbial growth. Metronidazole was not reduced in resistant cells which remained metabolically active and with their entire genetic material throughout the experiment. On the other hand, susceptible cells presented chromosomal breakage, a rapid consumption of dissolved metronidazole and a mortality of 90% of the bacterial population during the first 30 minutes of exposure. This interaction between metronidazole and DNA molecules that suggests strands breakage has been previously demonstrated in cell-free extract and in Escherichia coli cells. Our results show this phenomenon also occurring inBacteroides group what was not previously observed in the literature.