Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

• DOI: 10.1016/j.xcrm.2022.100656
• Publication Date: 2022-06-21T14:52:54Z
• Authors: Michelle S. Bach; Christiaan R. de ...; Arya Khosravi; Johanna M. Sweere; Medeea C. Popescu; Qingquan Chen; Sally Demirdjian; Aviv Hargil; Jonas D. Van Bell...; Gernot Kaber; Maryam Hajfathalian; Elizabeth B. Burg...; Dan Liu; Quynh-Lam Tran; Tejas Dharmaraj; Maria Birukova; Vivekananda Sunkari; Swathi Balaji; Nandini Ghosh; Shomita S. Mathew...; Mohamed S. El Masry; Sundeep G. Keswani; Niaz Banaei; Laurence Nedelec; Chandan K. Sen; Venita Chandra; Patrick R. Secor; Gina A. Suh; Paul L. Bollyky
• Keywords: Mammals; Filamentous phage; Wound Healing; 0303 health sciences; Immunology; Microbiology; 3. Good health; 03 medical and health sciences; Inovirus; Report; Biofilms; Pseudomonas; Wounds; Pseudomonas aeruginosa; Wound Infection; Animals; Humans; Pseudomonas Infections; Prospective Studies; Bacteriophage

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.