AMR in Mono and Polymicrobial Biofilm-Associated Infection

AMR in Mono and Polymicrobial Biofilm-Associated Infection

Antimicrobial-tolerant E. faecalis (red) biofilm proliferating within an infective endocarditis vegetation. Inset depicts the entire vegetation. Confocal laser scanning microscopy (CLSM) reveals dense, treatment-refractory biofilm embedded within the infected tissue. False-colored inset shows the full vegetation. (H. Antypas)

Biofilms are structured microbial communities encased in an extracellular matrix that provide both physical and physiological protection from environmental stressors, including the host immune system and antibiotic treatment. Enterococcus faecalis readily forms biofilms on medical devices and damaged host tissues, contributing to chronic infections such as catheter-associated urinary tract infection, wound infection, and endocarditis. These infections are notoriously difficult to treat, in large part due to the altered antimicrobial tolerance associated with biofilm growth.

Our research focuses on understanding how E. faecalis establishes and maintains biofilm communities, both as a single species and in polymicrobial settings with co-occurring pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. We study how biofilm architecture, metabolism, and signaling pathways contribute to augmented virulence and antimicrobial resilience, including non-heritable mechanisms of tolerance that differ from classical resistance. In polymicrobial biofilms, we are particularly interested in how interspecies interactions influence drug susceptibility and therapeutic failure.

Using a combination of in vitro biofilm models, in vivo infection systems, transcriptomics, and forward genetic screens, we identify bacterial and community-level factors that mediate biofilm-associated antimicrobial tolerance and immune evasion. These insights help inform the design of more effective treatment strategies that target the unique biology of biofilm-associated infections and mitigate the impact of antimicrobial resistance (AMR) in complex infection settings.