Biofilm Formation Mechanisms of Pseudomonas aeruginosa Predicted via Genome-Scale Kinetic Models of Bacterial Metabolism

• DOI: 10.1371/journal.pcbi.1004452
• Publication Date: 2015-10-02T18:04:23Z
• Authors: Francisco G. Vita...; Jaques Reifman; Anders Wallqvist
• Keywords: Flux Balance Analysis

A hallmark of Pseudomonas aeruginosa is its ability to establish biofilm-based infections that are difficult eradicate. Biofilms less susceptible host inflammatory and immune responses have higher antibiotic tolerance than free-living planktonic cells. Developing treatments against biofilms requires an understanding bacterial biofilm-specific physiological traits. Research efforts started elucidate the intricate mechanisms underlying biofilm development. However, many aspects these still poorly understood. Here, we addressed questions regarding metabolism using a genome-scale kinetic model P. metabolic network gene expression profiles. Specifically, computed metabolite concentration differences between known mutants with altered formation wild-type strain predict drug targets biofilms. We also simulated driven by changes stationary growth-phase cultures. Our analysis suggests synthesis important biofilm-related molecules, such as quorum-sensing molecule quinolone signal exopolysaccharide Psl, regulated not only through genes in their own pathway, but pathways competing for precursors molecules. Finally, investigated why defective anthranilate degradation impaired form Alternative previous hypothesis this reduction caused decrease energy production, proposed dysregulation secondary metabolites derived from chorismate what mutants. Notably, insights generated our model-based approach accessible constraint-based analyses metabolism. simulation results showed plausible, non-intuitive explanations difficult-to-interpret experimental observations could be integrating models