Abstract
Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.
Highlights
Pseud omonas aeruginosa (Pa) is a major human pathogen associated with chronic infections in wounds, burns, and nosocomial settings [1,2,3,4,5]
Pa infections are highly problematic in cystic fibrosis (CF), an inherited disease associated with defective ion transport and the accumulation of thick, tenacious airway secretions
Pf virions could benefit Pa infecting CF airways by reducing bacterial clearance from the lung. Consistent with this idea, Pa superinfected by Pf established a non-invasive infection phenotype in a mouse model of pneumonia and did not disseminate from the lung whereas Pa not producing Pf virions disseminated to distal tissues, suggesting that Pf phages contribute to the establishment of conditions that promote localized chronic infection [112]
Summary
Pseud omonas aeruginosa (Pa) is a major human pathogen associated with chronic infections in wounds, burns, and nosocomial settings [1,2,3,4,5]. Pa is responsible for extensive mortality and billions of dollars in health care costs [6,7,8]. Pa was recently listed as a critical priority pathogen by the World health Organization (WHO) [9]
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