A mathematical model of quorum quenching in biofilm colonies and its potential role as an adjuvant for antibiotic treatment

Abstract

We extend a previously presented mesoscopic (i.e. colony scale) mathematical model of the reaction of bacterial biofilms to antibiotics. In that earlier model, exposure to antibiotics evokes two responses: inactivation as the antibiotics kill the bacteria, and inducing a quorum sensing based stress response mechanism upon exposure to small sublethal dosages. To this model we add now quorum quenching as an adjuvant to antibiotic therapy. Quorum quenchers are modeled like enzymes that degrade the quorum sensing signal concentration. The resulting model is a quasilinear system of seven reaction-diffusion equations for the dependent variables volume fractions of upregulated (protected), downregulated (unprotected) and inert (inactive) biomass [particulate substances], and for concentrations of a growth promoting nutrient, antibiotics, quorum sensing signal, and quorum quenchers [dissolved substances]. The biomass fractions are subject to two nonlinear diffusion effects: (i) degeneracy, as in the porous medium equation, where biomass vanishes, and (ii) a super-diffusion singularity where as it attains its theoretically possible maximum. We study this model in numerical simulations. Our simulations suggest that for maximum efficacy quorum quenchers should be applied early on before quorum sensing induction in the biofilm can take place, and that an antibiotic strategy that by itself might not be successful can be notably improved upon if paired with quorum quenchers as an adjuvant.

Keywords

• antibiotics, biofilm, mathematical model, nonlinear diffusion, quorum quenching, quorum sensing.