Exposure of Salmonella biofilms to antibiotic concentrations rapidly selects resistance with collateral tradeoffs

Trampari, Eleftheria, Holden, Emma R., Wickham, Gregory J., Ravi, Anuradha, Martins, Leonardo de Oliveira, Savva, George M. and Webber, Mark A. (2021) Exposure of Salmonella biofilms to antibiotic concentrations rapidly selects resistance with collateral tradeoffs. npj Biofilms and Microbiomes, 7. ISSN 2055-5008

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Abstract

Most bacteria in nature exist in biofilms, which are inherently tolerant to antibiotics. There is currently very limited understanding of how biofilms evolve in response to sub-lethal concentrations of antimicrobials. In this study, we use a biofilm evolution model to study the effects of sub-inhibitory concentrations of three antibiotics on Salmonella Typhimurium biofilms. We show that biofilms rapidly evolve resistance to each antibiotic they are exposed to, demonstrating a strong selective pressure on biofilms from low antibiotic concentrations. While all antibiotics tested select for clinical resistance, there is no common mechanism. Adaptation to antimicrobials, however, has a marked cost for other clinically important phenotypes, including biofilm formation and virulence. Cefotaxime selects mutants with the greatest deficit in biofilm formation followed by azithromycin and then ciprofloxacin. Understanding the impacts of exposure of biofilms to antibiotics will help understand evolutionary trajectories and may help guide how best to use antibiotics in a biofilm context. Experimental evolution in combination with whole-genome sequencing is a powerful tool for the prediction of evolution trajectories associated with antibiotic resistance in biofilms.

Item Type: Article
Additional Information: Data availability statement: Whole-genome sequencing data that support the findings of this study have been deposited in the Sequence Read Archive with the project number PRJNA529870 Code availability: All software used is described in the ‘Methods’ and the data and code used for analysis that support findings of this study are freely available online (https://github.com/quadram-institute-bioscience/2020.Salmonella_biofilm/blob/master/tidy_snps.ipynb). Funding Information: The author(s) gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); E.T., A.R. and M.A.W. were supported by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10349. L.d.O.M. and G.M.S. were supported by the Quadram Institute Bioscience BBSRC funded Core Capability Grant (project number BB/CCG1860/1). Bioinformatics analyses were performed on CLIMB-computing servers, an infrastructure supported by a grant from the UK Medical Research Council (MR/L015080/1).
Uncontrolled Keywords: biotechnology,microbiology,applied microbiology and biotechnology ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School:
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Science > Research Groups > Norwich Epidemiology Centre
Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre
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Depositing User: LivePure Connector
Date Deposited: 21 Jan 2021 00:55
Last Modified: 04 Nov 2024 13:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/78245
DOI: 10.1038/s41522-020-00178-0

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