Chromosomal breakage in the B-fragilis group induced by metronidazole treatment

Metronidazole is used in clinical practice for the treatment of protozoan a nd anaerobic infections. Under anaerobic conditions, 5-nitroimidazoles are reduced to cytotoxic nitroradicals which have been shown to act by nonspeci fic binding to, and inactivation of the organism's DNA and enzymes. Among a naerobes, the Bacteroides fragilis group is the most relevant both in terms of frequency of isolation and antimicrobial resistance. In the present stu dy we investigated the mechanism of action of metronidazole in the B. fragi lis group. We evaluated chromosomal DNA integrity in susceptible and resist ant strains during a period of 5 h after metronidazole exposure and we quan tified the drug remaining in the medium after microbial growth. Metronidazo le was not reduced in resistant cells which remained metabolically active a nd with their entire genetic material throughout the experiment. On the oth er hand, susceptible cells presented chromosomal breakage, a rapid consumpt ion of dissolved metronidazole and a mortality of 90% of the bacterial popu lation during the first 30 minutes of exposure. This interaction between me tronidazole and DNA molecules that suggests strands breakage has been previ ously demonstrated in cell-free extract and in Escherichia coli cells. Our results show this phenomenon also occurring in Bacteroides group what was n ot previously observed in the literature. (C) 2000 Academic Press.