Mechanism of Action of Metronidazole on Bacteroides fragilis

Metronidazole (10 micrograms/ml) was rapidly bactericidal when added to log-phase cultures of Bacteroides fragilis strain 2624. DNA synthesis stopped immediately after addition of metronidazole, whereas synthesis of RNA and protein continued at linear rates for at least 60 min. Gel electrophoresis of DNA extracted from metronidazole-treated cells revealed no nicking or strand breakage in either the 2.9- or 2.0-megadalton plasmid of strain 2624. Also, no degradation of chromosomal DNA was seen. DNA polymerase activity, measured in vitro, was not diminished by prior treatment of the cells with metronidazole. Thus, the primary action of metronidazole is a rapid inhibition of DNA replication. The DNA remains structurally intact, DNA polymerase activity is not directly affected, and cells retain metabolic activity, synthesizing RNA and protein at unaltered rates.