A guide to the ecological limitations of phage therapy of bacterial biofilms: Is what's best for the phage best for the physician?

Bacterial biofilms-structured communities of bacteria encased in self-produced polymeric matrices-present formidable challenges in clinical medicine. The resistance of biofilms to conventional antibiotics stems from multiple factors. These include limited drug penetration and the presence of metabolically dormant bacteria that survive treatments, despite their retaining sensitivity under standard laboratory conditions. Bacteriophages (phages), the viruses that infect and kill bacteria, have emerged as promising alternatives or adjuncts to antibiotic therapy, including against bacterial biofilms. Phages, nonetheless, likely evolved to optimize especially their dissemination between spatially separated bacteria, including spatially separated biofilms, rather than to become specialists at eradicating all targeted bacteria from biofilms. By contrast, complete bacterial elimination from the body is the standard goal of antibacterial therapies. Considered here is how an understanding of these competing goals-virion dissemination vs. complete bacterial eradication-can inform our development of phage-based anti-biofilm therapies.