Abstract
BackgroundChronic wounds are often colonized by consortia comprised of different bacterial species growing as biofilms on a complex mixture of wound exudate. Bacteria growing in biofilms exhibit phenotypes distinct from planktonic growth, often rendering the application of antibacterial compounds ineffective. Computational modeling represents a complementary tool to experimentation for generating fundamental knowledge and developing more effective treatment strategies for chronic wound biofilm consortia.ResultsWe 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 demonstrate the tendency of the two bacteria to spatially partition in the multispecies biofilm as observed experimentally. 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. 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. 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 primarily to the more efficient lactate 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.ConclusionsOur biofilm modeling approach allows the prediction of individual species metabolism and interspecies interactions in both time and space with genome-scale resolution. This study yielded new insights into the multispecies metabolism of a chronic wound biofilm, in particular metabolic factors that may lead to spatial partitioning of the two bacterial species. We believe that P. aeruginosa lysis of S. aureus combined with nutrient competition is a particularly relevant scenario for which model predictions could be tested experimentally.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0334-8) contains supplementary material, which is available to authorized users.
Highlights
Chronic wounds are often colonized by consortia comprised of different bacterial species growing as biofilms on a complex mixture of wound exudate
We developed an effective computational method for solving the biofilm models, which consisted of a set of partial differential equations with mixed boundary conditions constrained by embedded linear programs
We developed genome-scale spatiotemporal models of a two species consortium comprised of the chronic wound isolates Pseudomonas aeruginosa and Staphylococcus aureus to investigate the impact of putative species interaction mechanisms on biofilm physiology
Summary
Chronic wounds are often colonized by consortia comprised of different bacterial species growing as biofilms on a complex mixture of wound exudate. The majority of bacteria grow as biofilms in mixed consortia that use mutualistic, syntrophic, commensal or antagonistic strategies to compete for and efficiently utilize available nutrients [1,2,3,4]. Microbial biofilms are critically important in medical, environmental and engineered biological systems. A major goal of current biofuels research is to engineer synthetic microbial communities that mimic these naturally occurring biofilms for biomass conversion to renewable liquid fuels [13]. While foundational to the vast majority of microbial life on the planet, the basic design principles of consortial biofilms are still poorly understood due largely to the complexity of naturally occurring systems [3, 4]
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