Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

• Published in: Cell reports. Medicine Vol. 3; no. 6; p. 100656
• Main Authors: Bach, Michelle S., de Vries, Christiaan R., Khosravi, Arya, Sweere, Johanna M., Popescu, Medeea C., Chen, Qingquan, Demirdjian, Sally, Hargil, Aviv, Van Belleghem, Jonas D., Kaber, Gernot, Hajfathalian, Maryam, Burgener, Elizabeth B., Liu, Dan, Tran, Quynh-Lam, Dharmaraj, Tejas, Birukova, Maria, Sunkari, Vivekananda, Balaji, Swathi, Ghosh, Nandini, Mathew-Steiner, Shomita S., El Masry, Mohamed S., Keswani, Sundeep G., Banaei, Niaz, Nedelec, Laurence, Sen, Chandan K., Chandra, Venita, Secor, Patrick R., Suh, Gina A., Bollyky, Paul L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2022; Elsevier
• Subjects: Animals; bacteriophage; Biofilms; filamentous phage; Humans; immunology; Inovirus; Mammals; microbiology; Prospective Studies; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections - therapy; Wound Healing; Wound Infection - therapy; wounds; wounds; Pf; microbiology; Pseudomonas; bacteriophage; immunology; filamentous phage
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100656

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. [Display omitted] •Pf, a bacteriophage produced by Pseudomonas aeruginosa, delays chronic wound healing•Pf impairs re-epithelization and barrier integrity in animal wound models•Pf inhibits keratinocyte signaling of CXCL1, contributing to impaired cell migration•Pf is associated with delayed healing in patients with chronic wound infections Wounds chronically infected by P. aeruginosa are characterized by poor healing and progression of disease. Bach et al. report that Pf, a bacteriophage expressed by P. aeruginosa, impedes healing by directly inhibiting keratinocyte chemokine expression migration, resulting in impaired wound re-epithelization.