Simulation-Based Exploration of Quorum Sensing Triggered Resistance of Biofilms to Antibiotics

We present a mathematical model of biofilm response to antibiotics, controlled by a quorum sensing system that confers increased resistance. The model is a highly nonlinear system of partial differential equations that we investigate in computer simulations. Our results suggest that an adaptive, quorum sensing-controlled, mechanism to switch between modes of fast growth with little protection and protective modes of slow growth may confer benefits to biofilm populations. It enhances the formation of micro-niches in the inner regions of the biofilm in which bacteria are not easily reached by antibiotics. Whereas quorum sensing inhibitors can delay the onset of increased resistance, their advantage is lost after up-regulation. This emphasizes the importance of timing for treatment of biofilms with antibiotics.