Spatiotemporal Metabolic Modeling of a Chronic Wound Biofilm Consortium*

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 a spatiotemporal model to analyze 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 model was able to provide both temporal and spatial predictions with genome-scale resolution. The model was used to analyze the metabolic differences between single species and multispecies biofilms and to demonstrate the tendency of the two bacteria to spatially partition due to nutrient gradients. The model predicted that S. aureus would dominant throughout the biofilm, especially in the anaerobic region where P. aeruginosa had very low growth rates. Lactate secreted by S. aureus and consumed by both species was predicted to further diminish P. aeruginosa competitiveness due to its lower cell densities. Lysis of S. aureus by inhibitors secreted from P. aeruginosa was predicted to enhance spatial partitioning of the two species and to substantially enhance the competitiveness of P. aeruginosa in partially aerobic regions of the biofilm interior.