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Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK

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Title: Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK
Authors: Wan, Y
Mills, E
Leung, RCY
Vieira, A
Zhi, X
Croucher, NJ
Woodford, N
Jauneikaite, E
Ellington, MJ
Sriskandan, S
Item Type: Journal Article
Abstract: 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 nitrofurantoin-resistant urinary E. coli isolates, as well as all further 11 E. coli isolates that were experimentally validated to be nitrofurantoin resistant. Eight categories of allelic changes in nfsA, nfsB, and the associated gene ribE were detected in 12,412 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 12,412 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.
Issue Date: 3-Dec-2021
Date of Acceptance: 2-Oct-2021
URI: http://hdl.handle.net/10044/1/92569
DOI: 10.1099/mgen.0.000702
ISSN: 2057-5858
Publisher: Microbiology Society
Start Page: 1
End Page: 19
Journal / Book Title: Microbial Genomics
Volume: 7
Issue: 12
Copyright Statement: © 2021 The Authors This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: HPRU-2012-10047
HPRU-2012-10047
RDA02
RDF04
Keywords: 0604 Genetics
0605 Microbiology
Publication Status: Published
Online Publication Date: 2021-12-03
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine
School of Public Health



This item is licensed under a Creative Commons License Creative Commons