Mathematical modelling of quorum sensing and its inhibition in Staphylococcus aureus

StaphylocoCCllS alirellS is a pathogenic bacterium which utilises quorum sensing (QS), a cell-to-cell signalling mechanism, to enhance its ability to cause disease. QS allows the bacteria to detect the size of their population and S. aureus manipulates this to regulate the production of virulence factors. In light of the emergence of multi-antibiotic resistant strains of S. allreus, its QS system, which is controlled by the agr operon, has been presented as a target for future therapies. For this to happen, the agr operon must be understood as comprehensively as possible. We describe a mathematical model of this QS network, incorporating various methods of inhibition, namely by synthetic inhibitor molecules, cross-strain inhibition and finally inhibition by the bacterium Pseudomol/ as aeruginosa. The full details of the protein interactions forming this QS circuit are not yet known and, given the ease of testing hypotheses mathematically as opposed to experimentally, we propose three different models which complete the possibilities for the agr operon. Through a combination of asymptotic and numerical methods, we compare these three models and their susceptibility to inhibition, and indicate differences in their behaviour which could be either verified or invalidated experimentally in order to provide insight into the correct biological details of the agr operon. We believe this to be the first full model of the agr operon and hope that it will shed light on staphylococcal QS and its potential use as a therapeutic target, as well as on some of the possible interactions between the signalling systems of diverse bacterial species.EThOS - Electronic Theses Online ServiceGBUnited Kingdo