The effect of antibiotic selection on collateral effects and evolvability of uropathogenic Escherichia coli

James, B, Reesaul, H, Kashif, S, Behruznia, M ORCID: https://orcid.org/0000-0002-3302-7272, Meehan, CJ ORCID: https://orcid.org/0000-0003-0724-8343, Domingo-Sananes, MR ORCID: https://orcid.org/0000-0002-3339-8671 and Hubbard, ATM ORCID: https://orcid.org/0000-0001-6668-9179, 2024. The effect of antibiotic selection on collateral effects and evolvability of uropathogenic Escherichia coli. npj Antimicrobials and Resistance, 2: 19. ISSN 2731-8745

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Abstract

Trimethoprim is recommended as a first-line treatment of urinary tract infections (UTIs) in the UK. In 2018, 31.4% of Escherichia coli isolated from UTIs in England were trimethoprim-resistant, leading to overreliance on other first and second-line antibiotics. Here, we assessed whether, in principle, prior selection with trimethoprim results in collateral effects to other antibiotics recommended for the treatment of UTIs. As collateral effects, we considered changes in susceptibility, mutation-selection window and population establishment probability. We selected 10 trimethoprim-resistant derivatives from three clinical isolates of uropathogenic Escherichia coli. We found that mutations conferring trimethoprim resistance did not have any collateral effects on fosfomycin. In contrast, resistance to trimethoprim resulted in decreased susceptibility (collateral resistance) to nitrofurantoin, below the clinical breakpoint and narrowed the mutation-selection window, thereby reducing the maximum concentration for selection of nitrofurantoin resistance mutations. Our analyses demonstrate that multiple collateral responses should be accounted for when predicting and optimising antibiotic use, limiting future antimicrobial resistance emergence.

Item Type:	Journal article
Publication Title:	npj Antimicrobials and Resistance
Creators:	James, B., Reesaul, H., Kashif, S., Behruznia, M., Meehan, C.J., Domingo-Sananes, M.R. and Hubbard, A.T.M.
Publisher:	Springer (part of Springer Nature)
Date:	2024
Volume:	2
ISSN:	2731-8745
Identifiers:	Number Type 10.1038/s44259-024-00037-4 DOI 1916023 Other
Rights:	© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	31 Jul 2024 08:45
Last Modified:	31 Jul 2024 08:45
URI:	https://irep.ntu.ac.uk/id/eprint/51858

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