Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines

Biological and structural characterization of the Mycobacterium smegmatis nitroreductase NfnB, and its role in benzothiazinone resistance

“…The genes acg , Rv0306 , moeY , fbiB , Rv3131 , Rv3127 , Rv3368c , Rv3547 , Rv1558 , Rv1261c , Rv3178 and lpdC were cloned into pSODIT‐2 expression vector, while Rv2337c gene was cloned with its own promoter region into pMD31 vector. All the recombinant clones were transformed into M. smegmatis and M. tuberculosis , and the MIC was evaluated both aerobically and anaerobically, as it is known that some bacterial NRs, including NfsB, need anaerobic conditions to reduce nitroaromatic compounds (Linwu et al ., 2009). None of the different M. tuberculosis NR had any effect on the MIC of BTZ043 in both species, irrespective of the conditions tested (Table S3).…”

Discovery and Characterization of a Nitroreductase Capable of Conferring Bacterial Resistance to Chloramphenicol

“…The oxygen-insensitive family of nitroreductases, such as those encoded by the nfsA or nfsB genes in E. coli, are known to be promiscuous reducers of aromatic nitro groups, and homologs of these genes are found across diverse bacterial taxa, including in many members of the intestinal microbiome (Roldá n et al, 2008). Nitro-reduction via these enzymes occurs two electrons at a time, often stopping at the production of a hydroxylamino group after a four-electron reduction (Roldá n et al, 2008), though some enzymes, such as the NfsB homologs from E. coli, Enterobacter cloacae, and Salmonella enterica, have been demonstrated to reduce aromatic nitro groups completely to amines (LinWu et al, 2009;Yanto et al, 2010) (Figure 1D). We found that expression of some of these genes in E. coli led to altered susceptibility/resistance to chloramphenicol.…”

Effects of bacterial and presystemic nitroreductase metabolism of 2-chloro-5-nitro-N-phenylbenzamide on its mutagenicity and bioavailability

“…Enteric bacteria are likely the most commonly responsible for metabolic reduction of drugs [27]. Rat and human intestinal bacteria have been shown to possess nitroreductase activity responsible for reduction of nitro containing drugs [28, 29]. Presystemic nitroreduction of GW9662 to ACPB by intestinal microflora would be consistent with this known bacterial nitroreductase activity and the above observations in the bacterial mutagenesis assay.…”