AN EXTENSION OF THE BOUNDARY INTEGRAL METHOD APPLIED TO PERIODIC DISINFECTION OF A DYNAMIC BIOFILM

Several tolerance mechanisms have been introduced to explain how bacterial biofilms are protected from disinfection. One mechanism describes the transition between two subpopulations of bacteria, one of which consumes nutrients, divides, and is susceptible to antimicrobial agents. The other subpopulation consists of dormant bacteria that are insensitive to treatments. It has been shown that the presence of this persister subpopulation can explain experimental observations of bacterial tolerance, at least in simplified domains. This investigation describes the development of a two-dimensional model of an established biofilm immersed in a flowing bulk fluid, where the biofilm influences the fluid dynamics and where the fluid flow can deform the biofilm. We introduce several extensions to this model, including the reaction between the biofilm and the antimicrobial agent, bacterial and exo-polymeric substance production, and persister dynamics. The model and numerical methods are based on the boundary integral method (BIM) but require extensions to the standard formulation to account for the production of mass within the biofilm. Our simulations indicate that many results from batch culture models carry over to the extended spatial domain. In particular, alternating dosing can eventually eliminate the bacteria but on a time scale that is much longer than in batch culture. We also predict that there is a heterogeneous distribution of persister cells that depends on the geometry of the biofilm and the dosing protocol.