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Antibiotics select for novel pathways of resistance in biofilms

Trampari, Eleftheria and Holden, Emma and Wickham, Gregory and Anuradha, Ravi and Prischi, Filippo and de Oliveira Martins, Leonardo and Savva, George and Bavro, Vassiliy N and Webber, Mark (2019) Antibiotics select for novel pathways of resistance in biofilms. Technical Report. bioRxiv.

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Abstract

Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response to sub-inhibitory concentrations of drugs. Here we used a biofilm evolution model to show that biofilms of a model food borne pathogen, Salmonella Typhimurium rapidly evolve in response to exposure to three clinically important antibiotics. Whilst the model strongly selected for improved biofilm formation in the absence of any drug, once antibiotics were introduced the need to adapt to the drug was more important than the selection for improved biofilm formation. Adaptation to antibiotic stress imposed a marked cost in biofilm formation, particularly evident for populations exposed to cefotaxime and azithromycin. We identified distinct resistance phenotypes in biofilms compared to corresponding planktonic control cultures and characterised new mechanisms of resistance to cefotaxime and azithromycin. Novel substitutions within the multidrug efflux transporter, AcrB were identified and validated as impacting drug export as well as changes in regulators of this efflux system. There were clear fitness costs identified and associated with different evolutionary trajectories. Our results demonstrate that biofilms adapt rapidly to low concentrations of antibiotics and the mechanisms of adaptation are novel. This work will be a starting point for studies to further examine biofilm specific pathways of adaptation which inform future antibiotic use.

Item Type: Monograph (Technical Report)
Uncontrolled Keywords: Microbiology, Antibiotic resistance, Structural biology, Biofilms
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 23 Oct 2019 13:03
Last Modified: 28 Jun 2021 14:15
URI: http://repository.essex.ac.uk/id/eprint/25693

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