A 3D numerical study of antimicrobial persistence in heterogeneous multi-species biofilms

Abstract

We develop a 3D hydrodynamic model to investigate the mechanism of antimicrobial persistence in a multi-species oral biofilm and its recovery after being treated by bisbiguanide chlorhexidine gluconate (CHX). In addition to the hydrodynamic transport in the spatially heterogeneous biofilm, the model also includes mechanisms of solvent-biomass interaction, bacterial phenotype conversion, and bacteria-drug interaction. A numerical solver for the model is developed using a second order numerical scheme in 3D space and time and implemented on GPUs. The model is calibrated against a set of experimental data obtained using confocal laser scan microscopy (CLSM) on a multi-species oral biofilm, where a quantitative agreement is reached. Our numerical results reveal that quorum sensing molecules and growth factors in this model are instrumental in biofilm formation and recovery after the antimicrobial treatment. In particular, we show that (i). young biofilms are more susceptible to the antimicrobial treatment than the mature ones, (ii). this phenomenon is strongly correlated with volume fractions of the persister and EPS in the biofilm being treated. This suggests that antimicrobial treatment be best administered to biofilms earlier before they mature to produce a thick protective EPS layer. In addition, the numerical study also indicates that an antimicrobial effect can be achieved should a proper mechanism be devised to minimize the conversion of susceptible bacteria to persisters during and even after the treatment.