Analysis of adaptive response to dosing protocols for biofilm control

Abstract

Biofilms are sessile populations of microbes that live within a self-secreted matrix of extracellular polymers. They exhibit high tolerance to antimicrobial agents, and experimental evidence indicates that in many instances repeated doses of antimicrobials further reduce disinfection efficiency due to an adaptive stress response. In this investigation, a mathematical model of bacterial adaptation is presented consisting of an adapted-unadapted population system embedded within a moving boundary problem coupled to a reaction-diffusion equation. The action of antimicrobials on biofilms under different dosing protocols is studied both analytically and numerically. We find the limiting behavior of solutions under periodic and on-off dosing as the period is made very large or very small. High dosages often carry undesirable side effects so we specially consider low dosing regimes. Our results indicate that on-off dosing for small doses of biocide is more effective than constant dosing. Moreover, in a specific case, on-off dosing for short periods is again more effective regardless of the biocide dose. We also provide sufficient conditions for the eradication of biofilms under a constant dosing regime.