Mechanical Enhancement and Immune Resistance of Pathogenic Biofilms through Host-derived Material Incorporation

Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances (EPS). The components of EPS and their interaction play a key role in the dynamic response to external environments and protect the biofilm bacteria from mechanical stress, clinical antimicrobials, and the human immune system. We have recently found that collagen, a host-produced protein abundant in various infection sites, can be incorporated into the biofilm and protect the biofilm from host immune cells, however, the precise mechanism remains unclear. Using particle-tracking microrheology and SEM imaging, we characterized the impact of collagen incorporation on the biofilms of three human pathogens: Pseudomonas aeruginosa, Burkholderia pseudomallei, and Staphylococcus aureus. Our findings reveal that collagen incorporation leads to micro-scale structural changes and increases the mechanical stability of these pathogenic biofilms. Additionally, enzymatic degradation of collagen compromises biofilm mechanical integrity, disrupts microstructures, and makes the biofilms more vulnerable to immune clearance. These insights may inform new strategies for treating biofilm-associated infections without promoting antibiotic resistance.