Combining mutation and horizontal gene transfer in a within-host model of antibiotic resistance

• Main Authors: Benschop, J. (Author), Burgess, S. (Author), French, N.P (Author), Marshall, J.C (Author), Roberts, M.G (Author), Toombs-Ruane, L.J (Author)
• Format: Article
• Language: English
• Published: Elsevier Inc. 2021
• Subjects: animal; Animals; Anti-Bacterial Agents; Antibiotic controls; antibiotic resistance; Antibiotic resistance; Antibiotics; antiinfective agent; Antimicrobial resistance; Antimicrobial resistances; Article; Bacteria; Bacteria (microorganisms); bacterial growth; bacterial load; bacterial mutation; bacterial strain; bacterium; bacterium conjugation; Bifurcation diagram; biological model; Cell proliferation; coliform bacterium; controlled study; DNA; DNA replication; drug effect; Drug Resistance, Bacterial; Dynamical systems; Escherichia coli; gene transfer; Gene transfer; Gene Transfer, Horizontal; Genes; genetics; horizontal gene transfer; Horizontal gene transfer; Host Microbial Interactions; human; Humans; infection control; infection prevention; mathematical computing; mobile genetic element; Models, Biological; mutation; Mutation; nonhuman; plasmid; Plasmid dynamics; Plasmids; Prevention and controls; quinolone derivative; Reproduction numbers; Selection pressures; steady state; wild type
• Online Access: View Fulltext in Publisher

 Antibiotics are used extensively to control infections in humans and animals, usually by injection or a course of oral tablets. There are several methods by which bacteria can develop antimicrobial resistance (AMR), including mutation during DNA replication and plasmid mediated horizontal gene transfer (HGT). We present a model for the development of AMR within a single host animal. We derive criteria for a resistant mutant strain to replace the existing wild-type bacteria, and for co-existence of the wild-type and mutant. Where resistance develops through HGT via conjugation we derive criteria for the resistant strain to be excluded or co-exist with the wild-type. Our results are presented as bifurcation diagrams with thresholds determined by the relative fitness of the bacteria strains, expressed in terms of reproduction numbers. The results show that it is possible that applying and then relaxing antibiotic control may lead to the bacterial load returning to pre-control levels, but with an altered structure with regard to the variants that comprise the population. Removing antimicrobial selection pressure will not necessarily reduce AMR and, at a population level, other approaches to infection prevention and control are required, particularly when AMR is driven by both mutation and mobile genetic elements. © 2021