title: Filamentous Bacteriophage Produced by Pseudomonas aeruginosa Alters the Inflammatory Response and Promotes Noninvasive Infection In Vivo.
abstract: Pseudomonas aeruginosa is an important opportunistic human pathogen that lives in biofilm-like cell aggregates at sites of chronic infection, such as those that occur in the lungs of patients with cystic fibrosis and nonhealing ulcers. During growth in a biofilm, P. aeruginosa dramatically increases the production of filamentous Pf bacteriophage (Pf phage). Previous work indicated that when in vivo Pf phage production was inhibited, P. aeruginosa was less virulent. However, it is not clear how the production of abundant quantities of Pf phage similar to those produced by biofilms under in vitro conditions affects pathogenesis. Here, using a murine pneumonia model, we show that the production of biofilm-relevant amounts of Pf phage prevents the dissemination of P. aeruginosa from the lung. Furthermore, filamentous phage promoted bacterial adhesion to mucin and inhibited bacterial invasion of airway epithelial cultures, suggesting that Pf phage traps P. aeruginosa within the lung. The in vivo production of Pf phage was also associated with reduced lung injury, reduced neutrophil recruitment, and lower cytokine levels. Additionally, when producing Pf phage, P. aeruginosa was less prone to phagocytosis by macrophages than bacteria not producing Pf phage. Collectively, these data suggest that filamentous Pf phage alters the progression of the inflammatory response and promotes phenotypes typically associated with chronic infection.
authors: Department of Microbiology, University of Washington, Seattle, Washington, USA psecor@uw.edu.
authors: Patrick R
authors: PR
authors: Secor
authors: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors: Lia A
authors: LA
authors: Michaels
authors: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors: Kate S
authors: KS
authors: Smigiel
authors: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors: Maryam G
authors: MG
authors: Rohani
authors: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors: Laura K
authors: LK
authors: Jennings
authors: Department of Microbiology, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Katherine B
authors: KB
authors: Hisert
authors: Benaroya Research Institute, Seattle, Washington, USA.
authors: Allison
authors: A
authors: Arrigoni
authors: Benaroya Research Institute, Seattle, Washington, USA.
authors: Kathleen R
authors: KR
authors: Braun
authors: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors: Timothy P
authors: TP
authors: Birkland
authors: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Ying
authors: Y
authors: Lai
authors: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Teal S
authors: TS
authors: Hallstrand
authors: Department of Medicine, Stanford University, Stanford, California, USA.
authors: Paul L
authors: PL
authors: Bollyky
authors: Department of Microbiology, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Pradeep K
authors: PK
authors: Singh
authors: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors: William C
authors: WC
authors: Parks
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development; D003550:Cystic Fibrosis / Q000382:microbiology / Q000821:virology; D007249:Inflammation / Q000382:microbiology* / Q000821:virology*; D017912:Inovirus / Q000254:growth & development*; D008168:Lung / Q000382:microbiology / Q000821:virology; D008264:Macrophages / Q000382:microbiology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000502:physiology; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000821:virology*; D011550:Pseudomonas aeruginosa / Q000821:virology*
keywords: Pseudomonas aeruginosa; bacteriophages; cystic fibrosis; dissemination; inflammation; lung infection; macrophages; neutrophils