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.