Catabolic pathway for 2-nitroimidazole involves a novel nitrohydrolase that also confers drug resistance.
Antibiotic resistance in pathogens can be mediated by catabolic enzymes thought to originate from soil bacteria, but the physiological functions and evolutionary origins of the enzymes in natural ecosystems are poorly understood. 2-Nitroimidazole (2NI) is a natural antibiotic and an analogue of the synthetic nitroimidazoles used for treatment of tuberculosis, Chagas' disease and cancer. Mycobacterium sp. JS330 was isolated from soil based on its ability to use 2NI as a sole growth substrate. The initial step in the degradation pathway is the hydrolytic denitration of 2NI to produce imidazol-2-one and nitrite. The amino acid sequence of 2NI nitrohydrolase is highly divergent from those of biochemically characterized enzymes, and it confers drug resistance when it is heterologously expressed in Escherichia coli. The unusual enzymatic reaction seems likely to determine the flux of nitroimidazole in natural ecosystems and also represents the discovery of a previously unreported drug resistance mechanism in soil before its identification in clinical situations.
School of Civil and Environmental Engineering, Georgia Institute of Technology, 311 Ferst Dr, Atlanta, GA 30332-0512, USA.
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D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015723:Gene Library; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D009593:Nitroimidazoles / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012988:Soil Microbiology
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009593:Nitroimidazoles; D006867:Hydrolases