Modeling antimicrobial tolerance and treatment of heterogeneous biofilms.
A multiphasic, hydrodynamic model for spatially heterogeneous biofilms based on the phase field formulation is developed and applied to analyze antimicrobial tolerance of biofilms by acknowledging the existence of persistent and susceptible cells in the total population of bacteria. The model implements a new conversion rate between persistent and susceptible cells and its homogeneous dynamics is bench-marked against a known experiment quantitatively. It is then discretized and solved on graphic processing units (GPUs) in 3-D space and time. With the model, biofilm development and antimicrobial treatment of biofilms in a flow cell are investigated numerically. Model predictions agree qualitatively well with available experimental observations. Specifically, numerical results demonstrate that: (i) in a flow cell, nutrient, diffused in solvent and transported by hydrodynamics, has an apparent impact on persister formation, thereby antimicrobial persistence of biofilms; (ii) dosing antimicrobial agents inside biofilms is more effective than dosing through diffusion in solvent; (iii) periodic dosing is less effective in antimicrobial treatment of biofilms in a nutrient deficient environment than in a nutrient sufficient environment. This model provides us with a simulation tool to analyze mechanisms of biofilm tolerance to antimicrobial agents and to derive potentially optimal dosing strategies for biofilm control and treatment.
Department of Mathematics, University of South Carolina, Columbia, SC 29208, USA; Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: zhaojia@live.unc.edu.
Jia
J
Zhao
Department of Mathematics, University of South Carolina, Columbia, SC 29208, USA.
Paisa
P
Seeluangsawat
Department of Mathematics, University of South Carolina, Columbia, SC 29208, USA; Beijing Computational Science Research Center, Beijing 100083, China; School of Mathematics, Nankai University, Tianjin 300071, China.
Qi
Q
Wang
D000890:Anti-Infective Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004361:Drug Tolerance; D008954:Models, Biological
D000890:Anti-Infective Agents
Biofilms; Hydrodynamics; Persister; Phase field