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

• Biofilm model integrates major HGT routes with phages, metal, and antibiotic dynamics. • Transduction and phage-induced decay are modelled as a saturated process. • Transduction spreads plasmids at much lower rates than conjugation or transformation. • Phage-induced lysis increases stress, favoring metabolically advantaged species. • Plasmid resistance enhances biofilm resilience, while phages lower antibiotic demand. The spread and control of antibiotic resistance is a major public health issue and challenge to address. This has driven a growing interest in bacteriophages, used alone or in combination with antibiotics to treat antibiotic-resistant biofilms. Evaluating the potential of phage therapy requires a detailed understanding of phages-microbes interactions, from their lytic activity to their capacity for transducing resistance genes. Mathematical models are a powerful tool to investigate specific aspects of these complex mechanisms, where a great number of biotic and abiotic interactions are involved. We present here a mathematical model exploring the role of phages in biofilm ecosystems 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. Numerical simulations investigate the contribution of vertical and horizontal gene transfer, including generalised transduction, to the spread of plasmid-mediated resistance. We assess the potential of phage therapy, both as a stand-alone treatment and in combination with antibiotics, highlighting how phage-antibiotic synergy can substantially reduce the antibiotic concentration required to eradicate even resistant biofilms. The simulations reveal how phage predation contributes to selective pressure and shapes biofilm ecology.