Filamentous Bacteriophage Delay Healing of Pseudomonas-Infected Wounds
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 reepithelialization, 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.