Dynamics of AMR beyond a single bacterial strain: Revealing the existence of multiple equilibria and immune system-dependent transitions

Abstract

The surge in antimicrobial resistance (AMR) is a critical global public health concern that complicates the eradication of harmful microorganisms within the host. Therefore, mathematical models have enhanced our understanding of AMR dynamics and aided in identifying measures to combat bacterial diseases, primarily focusing on single bacterial strains rather than microbial consortia. However, microbial consortia have not been extensively investigated. This study is a significant effort to examine the transmission of resistance in microbial communities, with a special focus on the ecological dynamics of microbial competition and the role of the host immune system in eradicating infections. We propose a mathematical model of AMR propagation that considers competition between two bacterial strains of the same species. Our analysis focuses on stability studies and the existence of bifurcations using different parameter values to represent the rate at which the host immune system eliminates bacteria. Our findings revealed that AMR propagation is primarily influenced by bacterial replication rate and host immune system efficacy. We observed that bacteria with lower replication rates could be effectively controlled, leading to disease extinction, whereas those with higher replication rates required a significantly robust immune response for clearance. The model demonstrated the existence of nine biologically feasible equilibrium points, with four explicitly associated with the different types of host immune systems characterized in the literature. Therefore, our study highlights the interplay between bacterial competition, immune system effectiveness, and AMR spread. We emphasize the importance of maintaining a robust immune system and establishing sensible antibiotic usage guidelines to slow the development and spread of antibiotic resistance.