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Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings

Ogunlana, Lois; Kaur, Divjot; Shaw, Liam P.; Jangir, Pramod; Walsh, Timothy; Uphoff, Stephan; MacLean, R. C.

Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings Thumbnail


Authors

Lois Ogunlana

Divjot Kaur

Pramod Jangir

Timothy Walsh

Stephan Uphoff

R. C. MacLean



Abstract

Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene that confers resistance to colistin, an agricultural antibiotic that is used as a last resort for the treatment of multi-drug resistant infections. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E. coli to reduce the fitness cost of mcr-1 while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low-cost/high-resistance mcr-1 alleles across an incredible diversity of E. coli strains, further stabilising mcr-1 at the species level. Regulatory mutations were associated with increased mcr-1 stability in pig farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how regulatory evolution and plasmid transfer can combine to stabilise resistance and limit the impact of reducing antibiotic consumption.

Citation

Ogunlana, L., Kaur, D., Shaw, L. P., Jangir, P., Walsh, T., Uphoff, S., & MacLean, R. C. (2023). Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings. The ISME Journal: Multidisciplinary Journal of Microbial Ecology, 17(11), 2058-2069. https://doi.org/10.1038/s41396-023-01509-7

Journal Article Type Article
Acceptance Date Sep 1, 2023
Online Publication Date Sep 18, 2023
Publication Date 2023-11
Deposit Date Oct 25, 2023
Publicly Available Date Oct 25, 2023
Journal The ISME Journal
Print ISSN 1751-7362
Electronic ISSN 1751-7370
Publisher Springer Nature
Peer Reviewed Peer Reviewed
Volume 17
Issue 11
Pages 2058-2069
DOI https://doi.org/10.1038/s41396-023-01509-7
Public URL https://durham-repository.worktribe.com/output/1807787

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http://creativecommons.org/licenses/by/4.0/

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Copyright Statement
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. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.





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