Imperial College London
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ProfessorShiraneeSriskandan

Faculty of Medicine, Department of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

s.sriskandan

 
 
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Assistant

 

Ms Teyanna Gaeta +44 (0)20 3313 1943

 
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Location

 

8N21ACWBCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wan:2021:10.1099/mgen.0.000702,
author = {Wan, Y and Mills, E and Leung, RCY and Vieira, A and Zhi, X and Croucher, NJ and Woodford, N and Jauneikaite, E and Ellington, MJ and Sriskandan, S},
doi = {10.1099/mgen.0.000702},
journal = {Microbial Genomics},
pages = {1--19},
title = {Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK},
url = {http://dx.doi.org/10.1099/mgen.0.000702},
volume = {7},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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 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.
AU  - Wan,Y
AU  - Mills,E
AU  - Leung,RCY
AU  - Vieira,A
AU  - Zhi,X
AU  - Croucher,NJ
AU  - Woodford,N
AU  - Jauneikaite,E
AU  - Ellington,MJ
AU  - Sriskandan,S
DO  - 10.1099/mgen.0.000702
EP  - 19
PY  - 2021///
SN  - 2057-5858
SP  - 1
TI  - Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK
T2  - Microbial Genomics
UR  - http://dx.doi.org/10.1099/mgen.0.000702
UR  - https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000702
UR  - http://hdl.handle.net/10044/1/92569
VL  - 7
ER  -
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