(648c) Metabolic Modeling of Pseudomonas Aeruginosa and Staphylococcus Aureus Interactions in Multispecies Biofilms

Chronic wounds are often colonized by consortia comprised of different bacterial species growing as biofilms on a complex mixture of wound exudate. The spatial organization of biofilm consortia cause bacteria to exhibit phenotypes distinct from planktonic growth and often render the application of antibacterial compounds ineffective. We developed spatiotemporal models to investigate the multispecies metabolism of a biofilm consortium comprised of two common chronic wound isolates: the aerobe Pseudomonas aeruginosa and the facultative anaerobe Staphylococcus aureus. By combining genome-scale metabolic reconstructions with partial differential equations for metabolite diffusion, the models were able to provide both temporal and spatial predictions with genome-scale resolution. The models were used to analyze the metabolic differences between single species and two species biofilms and to investigate the tendency of the two bacteria to spatially partition in the multispecies biofilm as observed experimentally. The two species system was predicted to support a maximum biofilm thickness much greater than P. aeruginosa alone but slightly less than S.aureus alone, suggesting an antagonistic metabolic effect of P. aeruginosa on S. aureus. Nutrient gradients imposed by supplying glucose at the bottom and oxygen at the top of the biofilm induced spatial partitioning of the two species, with S. aureus most concentrated in the anaerobic region and P. aeruginosa present only in the aerobic region. When each species was allowed to enhance its growth through consumption of secreted metabolic byproducts assuming identical uptake kinetics, the competitiveness of P. aeruginosa was further reduced due to the more efficient glucose oxidative metabolism of S. aureus. Lysis of S. aureus by a small molecule inhibitor secreted from P. aeruginosa and/or P. aeruginosa aerotaxis were predicted to substantially increase P. aeruginosa competitiveness in the aerobic region, consistent with in vitro experimental studies.