title: 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 for high-performance computing. The model is calibrated against a set of experimental data obtained using confocal laser scan microscopy (CLSM) on multi-species oral biofilms, 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 should 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.
authors.affiliation: Department of Mathematics, University of South Carolina, Columbia, SC 29208, United States. Electronic address: zhao62@math.sc.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: yashen@dentistry.ubc.ca.
authors.forename: Ya
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: zhejun@dentistry.ubc.ca.
authors.forename: Markus
authors.initials: M
authors.lastname: Haapasalo
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: qwang@math.sc.edu.
authors.forename: Zhejun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Mathematics, Nankai University, Tianjin 300071, China; Department of Mathematics, University of South Carolina, Columbia, SC 29208, United States; Beijing Computational Science Research Center, Beijing 100094, China. Electronic address: qwang@math.sc.edu.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D059013:Microbial Consortia / Q000502:physiology*; D008954:Models, Biological; D053038:Quorum Sensing / Q000502:physiology*
keywords: Antimicrobial persistence; Biofilms; Hydrodynamics; Multiphase fluids