We have identified a novel role for filamentous bacteriophage in the delayed healing associated with chronic Pseudomonas aeruginosa (Pa) wound infections. In a mouse model of chronic Pa-infected wounds, Pf, a filamentous phage produced by Pa, impaired keratinocyte migration, prevented wound re-epithelialization, and delayed healing in both the absence and presence of live bacteria. Mechanistically, the immune response to Pf phage produces soluble factors that impair keratinocyte migration and delay wound re-epithelialization. In a prospective cohort study of 113 human patients, Pa was detected in 36 patients and 25 of these (69%) were positive for Pf phage. Pf(+) wounds were significantly older and more likely to increase in size over time than Pf(-) wounds. Together, these data implicate Pf in the delayed wound healing associated with Pa infection. We propose that Pf phage may have potential as a biomarker and therapeutic target for delayed wound healing.

Filamentous Bacteriophage Delay Healing of Pseudomonas-Infected Wounds