Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Michelle S. Bach, Christiaan R. de Vries, Arya Khosravi, Johanna M. Sweere, Medeea C. Popescu, Qingquan Chen, Sally Demirdjian, Aviv Hargil, Jonas D. Van Belleghem, Gernot Kaber, Maryam Hajfathalian, Elizabeth B. Burgener, Dan Liu, Quynh Lam Tran, Tejas Dharmaraj, Maria Birukova, Vivekananda Sunkari, Swathi Balaji, Nandini Ghosh, Shomita S. Mathew-SteinerMohamed S. El Masry, Sundeep G. Keswani, Niaz Banaei, Laurence Nedelec, Chandan K. Sen, Venita Chandra, Patrick R. Secor, Gina A. Suh, Paul L. Bollyky

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number100656
JournalCell Reports Medicine
Volume3
Issue number6
DOIs
StatePublished - Jun 21 2022

Keywords

  • Pf
  • Pseudomonas
  • bacteriophage
  • filamentous phage
  • immunology
  • microbiology
  • wounds

Fingerprint

Dive into the research topics of 'Filamentous bacteriophage delays healing of Pseudomonas-infected wounds'. Together they form a unique fingerprint.

Cite this