Mesoscopic Energy Minimization Drives Pseudomonas aeruginosa Biofilm Morphologies and Consequent Stratification of Antibiotic Activity Based on Cell Metabolism [PublishAheadOfPrint]

Segregation of bacteria based on their metabolic activity in biofilms plays an important role in the development of antibiotic drug resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explore the development of metabolically heterogenous Pseudomonas aeruginosa biofilms using numerical models and laboratory knock-out experiments on wild-type and chemotaxis deficient mutants. We show that chemotactic processes dominate the transformation of slender and hemispherical structures into mushroom structures with a signature cap. Cellular Potts model simulation and experimental data provide evidence that accelerated movement of bacteria along the periphery of the biofilm, due to nutrient cues, results in the formation of mushroom structures and bacterial segregation. Multi-drug resistance of bacteria is one of the most threatening dangers to public health. Understanding the mechanisms of the development of mushroom shaped biofilms helps to identify the multidrug resistant regions. We decoded the dynamics of the structural evolution of bacterial biofilms and the physics behind the formation of biofilm structures as well as the biological triggers that produce them. Combining in-vitro gene knock-out experiments with in-silico models shows that chemotactic motility is one of the main driving forces for the formation of stalks and caps. Our result provides physicists and biologists with a new perspective on biofilm removal and eradication strategies.

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