RT Journal Article SR Electronic(1) A1 Wan, Yu A1 Mills, Ewurabena A1 Leung, Rhoda C.Y. A1 Vieira, Ana A1 Zhi, Xiangyun A1 Croucher, Nicholas J. A1 Woodford, Neil A1 Jauneikaite, Elita A1 Ellington, Matthew J. A1 Sriskandan, ShiraneeYR 2021 T1 Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in Escherichia coli from the United Kingdom JF Microbial Genomics, VO 7 IS 12 OP SP 000702 DO https://doi.org/10.1099/mgen.0.000702 PB Microbiology Society, SN 2057-5858, AB Antimicrobial resistance in enteric or urinary   Escherichia coli   is a risk factor for invasive   E. coli   infections. Due to widespread trimethoprim resistance amongst urinary   E. coli   and increased bacteraemia incidence, a national recommendation to prescribe nitrofurantoin for uncomplicated urinary tract infection was made in 2014. Nitrofurantoin resistance is reported in <6% urinary   E. coli   isolates in the UK, however, mechanisms underpinning nitrofurantoin resistance in these isolates remain unknown. This study aimed to identify the genetic basis of nitrofurantoin resistance in urinary   E. coli   isolates collected from north west London and then elucidate resistance-associated genetic alterations in available UK   E. coli   genomes. As a result, an algorithm was developed to predict nitrofurantoin susceptibility. Deleterious mutations and gene-inactivating insertion sequences in chromosomal nitroreductase genes nfsA and/or nfsB were identified in genomes of nine confirmed nitrofurantoin-resistant urinary   E. coli   isolates and additional 11   E. coli   isolates that were highlighted by the prediction algorithm and subsequently validated to be nitrofurantoin-resistant. Eight categories of allelic changes in nfsA, nfsB, and the associated gene ribE were detected in 12412   E. coli   genomes from the UK. Evolutionary analysis of these three genes revealed homoplasic mutations and explained the previously reported order of stepwise mutations. The mobile gene complex oqxAB, which is associated with reduced nitrofurantoin susceptibility, was identified in only one of the 12412 genomes. In conclusion, mutations and insertion sequences in nfsA and nfsB were leading causes of nitrofurantoin resistance in UK   E. coli  . As nitrofurantoin exposure increases in human populations, the prevalence of nitrofurantoin resistance in carriage   E. coli   isolates and those from urinary and bloodstream infections should be monitored., UL https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000702