Streptococcus faecalis cells were sonically treated, and the extract of the treated cells was filtered through a 0.45-μm filter to remove the living organism. The cell-free extract was assayed for metronidazole-inactivating and nitroreductase activities, the latter being regarded as the inactivating factor.
Metronidazole, a nitroimidazole derivative, was rapidly inactivated in broth by the cell-free extract of S. faecalis as measured by GLC and bioassay. As the rate of inactivation varied depending upon the medium and as the inactivating activity of the cell-free filtrate was not detected in broth cultures of the organism, the activity may occasionally be overlooked. The inactivating factor was produced in either the absence or the presence of oxygen and not induced by metronidazole but a constituent factor.
The metronidazole-inactivating activity was detected also in cell-free extracts of Escherichia coli but not of Streptococcus agalactiae, Staphylococcus aureus or Serratia marcescens as was the case with the living organisms.
Nitroreductase activity was detected in the cell-free extracts of the microbes inactivating metronidazole, but not of those not inactivating the drug.
It is assumed that metronidazole is inactivated when its nitro-group is reduced by the action of nitroreductase in the cell-free extract of S. faecalis.