Metabolism of a 5-nitroimidazole in susceptible and resistant isogenic strains of Bacteroides fragilis.
We investigated the metabolism of dimetridazole (1,2-dimethyl-5-nitroimidazole) (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, under strict anaerobic conditions DMZ was metabolized without major ring cleavage or nitrate formation. However, one of two distinct metabolic pathways is involved, depending on the susceptibility of the strain. In the susceptible strain, the classical reduction pathway of nitroaromatic compounds is followed at least as far as the nitroso-radical anion, with further formation of the azo-dimer: 5,5'-azobis-(1,2-dimethylimidazole). In the resistant strain, DMZ is reduced to the amine derivative, namely, 5-amino-1,2-dimethylimidazole, preventing the formation of the toxic form of the drug. The specificity of the six-electron reduction of the nitro group, which is restricted to 4- and 5-nitroimidazole, suggests an enzymatic reaction. We thus conclude that nimA and related genes may encode a 5-nitroimidazole reductase.
Carlier
J P
JP
Unité des Anaérobies, Institut Pasteur, Paris, France. jcarlier@pasteur.fr
Sellier
N
N
Rager
M N
MN
Reysset
G
G
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001441:Bacteroides fragilis / Q000187:drug effects* / Q000235:genetics; D003001:Cloning, Molecular; D004131:Dimetridazole / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D005798:Genes, Bacterial; D005822:Genetic Vectors; D007093:Imidazoles / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics*
D000900:Anti-Bacterial Agents; D007093:Imidazoles; C050486:5-amino-1,2-dimethylimidazole; D004131:Dimetridazole