| Abstrakt: |
ABSTRACTFive spontaneous nitrofurantoin-resistant mutants (one each ofClostridium leptum, Clostridium paraputrificum, two other Clostridiumspp. strains from the human intestinal microflora, and Clostridium perfringensATCC 3626) were selected by growth on a nitrofurantoin-containing medium. All of the Clostridiumwild-type and mutant strains produced nitroreductase, as was shown by the conversion of 4-nitrobenzoic acid to 4-aminobenzoic acid. High-performance liquid chromatography (HPLC) analysis of the mutants during incubation with 50 μg of nitrofurantoin per ml showed the gradual disappearance of the nitrofurantoin peak. The nitrofurantoin peak also disappeared when cell-free supernatants instead of cultures of each of the resistant and wild-type bacteria were used, but it persisted if the cell-free supernatants had been inactivated by heat. At least two of the mutants converted nitrofurantoin to metabolites without antibacterial activity, as was shown by a bioassay with a nitrofurantoin-susceptibleBacillussp. strain. Nitrofurantoin at a high concentration (50 μg/ml) continued to exert some toxicity, even on the resistant strains, as was evident from the longer lag phases. This study indicates that Clostridiumstrains can develop resistance to nitrofurantoin while retaining the ability to produce nitroreductase; the mutants metabolized nitrofurantoin to compounds without antibacterial activity. |
