An Integrated Modeling and Experimental Approach to Study the Influence of Environmental Nutrients on Biofilm Formation ofPseudomonas aeruginosa

Abstract

The availability of nutrient components in the environment was identified as a critical regulator of virulence and biofilm formation inPseudomonas aeruginosa. This work proposes the first systems-biology approach to quantify microbial biofilm formation upon the change of nutrient availability in the environment. Specifically, the change of fluxes of metabolic reactions that were positively associated withP. aeruginosabiofilm formation was used to monitor the trend forP. aeruginosato form a biofilm. The uptake rates of nutrient components were changed according to the change of the nutrient availability. We found that adding each of the eleven amino acids (Arg, Tyr, Phe, His, Iso, Orn, Pro, Glu, Leu, Val, and Asp) to minimal medium promotedP. aeruginosabiofilm formation. Both modeling and experimental approaches were further developed to quantifyP. aeruginosabiofilm formation for four different availability levels for each of the three ions that include ferrous ions, sulfate, and phosphate. The developed modeling approach correctly predicted the amount of biofilm formation. By comparing reaction flux change upon the change of nutrient concentrations, metabolic reactions used byP. aeruginosato regulate its biofilm formation are mainly involved in arginine metabolism, glutamate production, magnesium transport, acetate metabolism, and the TCA cycle.