A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer

Arya, Sankalp; Todman, Henry; Baker, Michelle; Hooton, Steven; Millard, Andrew; Kreft, Jan Ulrich; Hobman, Jon L.; Stekel, Dov J.

Abstract

© FEMS 2020. Antimicrobial resistance is a major global challenge. Of particular concern are mobilizable elements that can transfer resistance genes between bacteria, leading to pathogens with new combinations of resistance. To date, mathematical models have largely focussed on transfer of resistance by plasmids, with fewer studies on transfer by bacteriophages. We aim to understand how best to model transfer of resistance by transduction by lytic phages. We show that models of lytic bacteriophage infection with empirically derived realistic phage parameters lead to low numbers of bacteria, which, in low population or localised environments, lead to extinction of bacteria and phage. Models that include antagonistic co-evolution of phage and bacteria produce more realistic results. Furthermore, because of these low numbers, stochastic dynamics are shown to be important, especially to spread of resistance. When resistance is introduced, resistance can sometimes be fixed, and at other times die out, with the probability of each outcome sensitive to bacterial and phage parameters. Specifically, that outcome most strongly depends on the baseline death rate of bacteria, with phage-mediated spread favoured in benign environments with low mortality over more hostile environments. We conclude that larger-scale models should consider spatial compartmentalisation and heterogeneous microenviroments, while encompassing stochasticity and co-evolution.

Citation

Arya, S., Todman, H., Baker, M., Hooton, S., Millard, A., Kreft, J. U., …Stekel, D. J. (2020). A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer. FEMS Microbiology Ecology, 96(7), https://doi.org/10.1093/femsec/fiaa100

• Journal Article Type: Article
• Acceptance Date: May 20, 2020
• Online Publication Date: Jun 3, 2020
• Publication Date: Jul 1, 2020
• Deposit Date: Jun 8, 2020
• Publicly Available Date: Jun 4, 2021
• Journal: FEMS microbiology ecology
• Print ISSN: 0168-6496
• Electronic ISSN: 1574-6941
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 96
• Issue: 7
• DOI: https://doi.org/10.1093/femsec/fiaa100
• Keywords: Ecology; Applied Microbiology and Biotechnology; Microbiology
• Public URL: https://nottingham-repository.worktribe.com/output/4597209
• Publisher URL: https://academic.oup.com/femsec/advance-article-abstract/doi/10.1093/femsec/fiaa100/5850753?redirectedFrom=fulltext
• Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in FEMS Microbiology Ecology following peer review. The version of record Sankalp Arya, Henry Todman, Michelle Baker, Steven Hooton, Andrew Millard, Jan-Ulrich Kreft, Jon L Hobman, Dov J Stekel, A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer, FEMS Microbiology Ecology, 96(7), is available online at: https://doi.org/10.1093/femsec/fiaa100