Metabolic modeling of a chronic wound biofilm consortium predicts spatial partitioning of bacterial species
Loading...
Date
2016-09
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
BACKGROUND: Chronic 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.
RESULTS: 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 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.
CONCLUSIONS: Our 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.
Description
Keywords
Citation
Phalak P, Chen J, Carlson RP, Henson MA “Metabolic modeling of a chronic wound biofilm consortium predicts spatial partitioning of bacterial species” BMC Syst Biol. 2016 Sep 7; 10(1):90.