Modelling the Role of Phages in Biofilm Ecosystems and the Spread of Antimicrobial Resistance

In this study, we present a mathematical model exploring the role of phages in biofilm ecosystems, with a focus on horizontal gene transfer via generalised transduction, phage-bacteria interactions, and the potential of phage therapy to eliminate resistant bacterial populations. The model is formulated as a system of non-local partial differential equations in a one-dimensional, free-boundary domain. It incorporates all major routes of horizontal gene transfer - conjugation, natural transformation, and generalised transduction - along with selective pressure from metals and antibiotics, within a spatially structured, growing biofilm. Transducing phages are generated as a consequence of a replication error during the infection of a plasmid-bearing cell by a lytic phage. Generalised transduction is modelled as a saturated process, resulting from the infection of a plasmid-free cell by a transducing phage, leading to plasmid recircularisation and conversion into a plasmid-carrying cell. Numerical simulations were performed to investigate the contribution of vertical and horizontal gene transfer, including generalised transduction, to the spread of plasmid-mediated resistance. The simulations also reveal the impact of phage predation on biofilm ecology, especially on plasmid persistence under environmental stress. The combined effects of metal toxicity and phage predation on the coexistence or extinction of plasmid-bearing and plasmid-free populations were assessed. Finally, the potential of phage therapy, both as a standalone treatment and in combination with antibiotics, was evaluated, revealing how phage-antibiotic synergy can substantially reduce the antibiotic concentration required to eradicate even resistant biofilms.