I have many questions about how the mechanics and microstructure of biofilm infections impact interactions with the immune system.

Biofilms are communities of microbes that are stuck together in aggregates by a matrix of polymers and proteins. Thus, a population of microbes in a biofilm state have viscoelastic properties that do not exist for the same population of bacteria that are suspended as individual cells in liquid culture. Biofilms also have biological properties that arise from the biofilm state – these include heightened tolerance of antibiotics and the inability of the immune system to clear infections in the form of biofilms, even though the same population of bacteria as individual cells would be very susceptible to antibiotics and easily engulfed by the immune system. As a result, biofilm infections are a major and increasing problem in healthcare in a wide range of scenarios.

The aggregates comprising biofilm infections are an order of magnitude larger in size than phagocytic immune cells. Therefore, for biofilm microbes to be cleared by phagocytosis, they must be separated from the biofilm. This must involve mechanical and structural compromise of the biofilm. Using abiotic gels as models to recreate biofilm mechanics, we have shown that the success of human neutrophils at engulfing things out of the gel is impacted by gel viscoelasticity and toughness. More recently, we have grown biofilms from two important human pathogens (Pseudomonas aeruginosa and Staphylococcus aureus) under conditions that mimic key physiological conditions. Differences in the mechanics and microstructure arise from the presence of collagen and calcium ions are linked to changes in the efficacy of human neutrophils at engulfing bacteria from the biofilm. Treatment of key matrix components, that takes into account chances induced by physiological components, can significantly increase the ability of neutrophils to engulf biofilm bacteria.

In future, we hope to extend this to a roadmap for designing specific treatments that compromise biofilm mechanics and microstructure to make them more susceptible to clearance by the immune system.