Understanding the transfer and persistence of antimicrobial resistance in aquaculture using a model teleost gut system

Authors: BARCAN, ALEXANDRU - University Of Glasgow; HUMBLE, JOSEPH - University Of Glasgow; KASARAGOD, SANDEEP - University Of Glasgow; SAJIB, MOHAMMAD - University Of Glasgow; BARCAN, RARES - University Of Strathclyde; MCGINNITY, PHILIP - University College Cork; Welch, Timothy - Tim; ROBERTSON, BRENDAN - University Of Glasgow; VAMANU, EMANUEL - University Of Agricultural Sciences And Veterinary Medicine - Romania; BACIGALUPO, ANTONELLA - University Of Glasgow; LLEWELLYN, MARTIN - University Of Glasgow; PEDRALS, FRANCISCA - University Of Sydney

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 8/12/2024
Publication Date: 8/30/2024
Citation: Barcan, A.S., Humble, J., Kasaragod, S., Sajib, M., Barcan, R.A., Mcginnity, P., Welch, T.J., Robertson, B., Vamanu, E., Bacigalupo, A., Llewellyn, M.S., Pedrals, F.S. 2024. Understanding the transfer and persistence of antimicrobial resistance in aquaculture using a model teleost gut system. bioRxiv. 605792. https://doi.org/10.1101/2024.07.30.605792.
DOI: https://doi.org/10.1101/2024.07.30.605792

Interpretive Summary: Antimicrobial resistance (AMR) presents a threat to both human and animal health as it reduces the effectiveness of treatment for many life-threatening bacterial diseases. Understanding the effect of antibiotic use on the amplification and spread of antibiotic resistance genes is critical for developing strategies that reduce or eliminate the transfer of resistance between bacteria. Herein, we describe the use of an Atlantic salmon artificial gut system (SalmoSim) to examine the effects of antibiotic use in feed on the spread and persistence of antibiotic resistance genes. Our results reveal that antibiotic treatment increased antibiotic gene transfer between bacteria and gene abundance in the test system and that AMR persisted beyond the antibiotic treatment phase of the experiment. In addition, our findings revealed that resistance gene transfer occurred in the absence of antibiotic use. This model system provides a resource to develop interventions to mitigate antibiotic gene transfer, amplification, and persistence.

Technical Abstract: The development, progression, and dissemination of antimicrobial resistance (AMR) is influenced by interlinked human, animal, and environmental ecosystems, posing severe risks to human health. Conjugative plasmid transfer drives the rapid dissemination of AMR among microbial populations. Mitigating antibiotic resistance spread requires an understanding of the dynamics of AMR transfer among microbial communities, as well as the role of various microbial taxa as potential reservoirs that promote long term AMR persistence. Here, we employed Hi-C, a high-throughput, culture-free technique, combined with qPCR, to monitor carriage and transfer of a multidrug-resistant plasmid within an Atlantic salmon in vitro gut model during florfenicol treatment, a benzenesulfonyl antibiotic widely deployed in fin-fish aquaculture. Microbial communities from the midgut (pyloric ceaca) of three healthy adult farmed salmon were inoculated into three bioreactors developed for the SalmoSim gut system. The model system was inoculated with an Escherichia coli strain ATCC 25922 carrying plasmid pM07-1 and treated with florfenicol at a concentration of 150 mg/L fish feed media for five days prior to a washout / recovery phase. Hi-C and metagenomic sequencing identified numerous transfer events, including Gram-negative and Gram-positive taxa and, crucially, widespread transfer and persistence of the plasmid in the absence of florfenicol. Our findings highlight the role of commensal teleost gut flora as a reservoir for AMR, and our system provides a model to study how different treatment regimes and interventions may be deployed to mitigate against AMR persistence.