METABOLISM OF A 5-NITROIMIDAZOLE IN SUSCEPTIBLE AND RESISTANT ISOGENIC STRAINS OF BACTEROIDES-FRAGILIS

We investigated the metabolism of dimetridazole (1,2-dimethyl-5-nitroi midazole) (DMZ) by the resting cell method in a susceptible strain of Bacteroides fragilis and in the same strain containing the nimA gene, which conferred resistance to 5-nitroimidazole drugs. In both cases, u nder strict anaerobic conditions DMZ was metabolized without major rin g cleavage or nitrate formation. However, one of two distinct metaboli c pathways is involved, depending on the susceptibility of the strain. In the susceptible strain, the classical reduction pathway of nitroar omatic compounds is followed at least as far as the nitroso-radical an ion, with further formation of the azo-dimer: 5,5'-azobis-(1,2-dimethy limidazole). In the resistant strain, DMZ is reduced to the amine deri vative, namely, 5-amino-1,2-dimethylimidazole, preventing the formatio n of the toxic form of the drug. The specificity of the six-electron r eduction of the nitro group, which is restricted to 4- and 5-nitroimid azole, suggests an enzymatic reaction. We thus conclude that nimA and related genes may encode a 5-nitroimidazole reductase.