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

M G Roberts1, S Burgess2, L J Toombs-Ruane2

  • 1School of Natural & Computational Sciences, Massey University, Private Bag 102 904, North Shore Mail Centre, Auckland, 0745, New Zealand; New Zealand Institute for Advanced Study, Massey University, Private Bag 102 904, North Shore Mail Centre, Auckland, 0745, New Zealand; Infectious Disease Research Centre, Massey University, Private Bag 11-222, Palmerston North, 4442, New Zealand.

Insights

Antimicrobial resistance (AMR) can develop in bacteria through mutation or horizontal gene transfer (HGT). Relaxing antibiotic use may not reduce AMR, necessitating alternative infection control strategies.

Area of Science:

  • Microbiology
  • Mathematical Biology
  • Epidemiology

Background:

  • Antibiotics are crucial for treating bacterial infections in humans and animals.
  • Antimicrobial resistance (AMR) develops via bacterial mutation or horizontal gene transfer (HGT).

Purpose of the Study:

  • To model the development of AMR within a single host animal.
  • To establish criteria for resistant bacterial strain replacement or co-existence with wild-type strains.
  • To analyze the impact of HGT on AMR dynamics.

Main Methods:

  • Development of a mathematical model for AMR evolution.
  • Derivation of criteria for strain replacement and co-existence using reproduction numbers.
  • Analysis of bifurcation diagrams to illustrate bacterial population dynamics.

Main Results:

  • Criteria were derived for resistant mutant replacement and co-existence with wild-type bacteria.
  • Conditions for exclusion or co-existence of resistant strains were determined for HGT via conjugation.
  • Results indicate that relaxing antibiotic pressure may not decrease AMR and can alter bacterial population structure.

Conclusions:

  • Removing antimicrobial selection pressure does not guarantee a reduction in AMR.
  • AMR dynamics are influenced by bacterial fitness, reproduction numbers, and HGT.
  • Integrated infection prevention and control strategies are essential, especially when AMR is driven by mutation and mobile genetic elements.

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