Development of the Pseudomonas aeruginosa mushroom morphology and cavity formation by iron-starvation: a mathematical modeling study.

We present a mathematical model of mushroom-like architecture and cavity formation in Pseudomonas aeruginosa biofilms. We demonstrate that a proposed disparity in internal friction between the stalk and cap extracellular polymeric substances (EPS) leads to spatial variation in volumetric expansion sufficient to produce the mushroom morphology. The capability of diffusible signals to induce the formation of a fluid-filled cavity within the cap is then investigated. We assume that conversion of bacteria to the planktonic state within the cap occurs in response to the accumulation or depletion of some signal molecule. We (a) show that neither simple nutrient starvation nor signal production by one or more subpopulations of bacteria is sufficient to trigger localized cavity formation. We then (b) demonstrate various hypothetical scenarios that could result in localized cavity formation. Finally, we (c) model iron availability as a detachment signal and show simulation results demonstrating cavity formation by iron starvation. We conclude that iron availability is a plausible mechanism by which fluid-filled cavities form in the cap region of mushroom-like structures.

Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung.

Lung failure due to chronic bacterial infection is the leading cause of death for patients with cystic fibrosis (CF). It is thought that the chronic nature of these infections is, in part, due to the increased tolerance and recalcitrant behaviour of bacteria growing as biofilms. Inhalation of silver carbene complex (SCC) antimicrobial, either encased in polymeric biodegradable particles or in aqueous form, has been proposed as a treatment. Through a coordinated experimental and mathematical modelling effort, we examine this proposed treatment of lung biofilms. Pseudomonas aeruginosa biofilms grown in a flow-cell apparatus irrigated with an artificial CF sputum medium are analysed as an in vitro model of CF lung infection. A 2D mathematical model of biofilm growth within the flow-cell is developed. Numerical simulations demonstrate that SCC inactivation by the environment is critical in aqueous SCC, but not SCC-polymer, based treatments. Polymer particle degradation rate is shown to be an important parameter that can be chosen optimally, based on environmental conditions and bacterial susceptibility.