Abstract
In persons with structural lung disease, particularly those with cystic fibrosis (CF), chronic airway infections cause progressive loss of lung function. CF airways can be colonized by a variety of microorganisms; the most frequently encountered bacterial and fungal pathogens are Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Co-infection with P. aeruginosa and A. fumigatus often results in a more rapid loss of lung function, indicating that interactions between these pathogens affect infection pathogenesis. There has been renewed interest in the use of viruses (bacteriophage, mycoviruses) as alternatives to antibiotics to treat these infections. In previous work, we found that filamentous Pf bacteriophage produced by P. aeruginosa directly inhibited the metabolic activity of A. fumigatus by binding to and sequestering iron. In the current study, we further examined how filamentous Pf bacteriophage affected interactions between P. aeruginosa and A. fumigatus. Here, we report that the antifungal properties of supernatants collected from P. aeruginosa cultures infected with Pf bacteriophage were substantially less inhibitory towards A. fumigatus biofilms. In particular, we found that acute infection of P. aeruginosa by Pf bacteriophage inhibited the production of the virulence factor pyoverdine. Our results raise the possibility that the reduced production of antimicrobials by P. aeruginosa infected by Pf bacteriophage may promote conditions in CF airways that allow co-infection with A. fumigatus to occur, exacerbating disease severity. Our results also highlight the importance of considering how the use of bacteriophage as therapeutic agents could affect the behavior and composition of polymicrobial communities colonizing sites of chronic infection.
Highlights
The airways of people with cystic fibrosis (CF) are persistently colonized by various opportunistic pathogens, the most prevalent being Pseudomonas aeruginosa (Pa) [1] and Aspergillus fumigatus (Af) [2]
Bacterial densities were comparable between Pa cultures not infected with Pf phage and cultures infected with Pf phage (Fig 1B)
This reduction in Af metabolic activity was observed in two strains of Pa infected with different strains of Pf phage (PAO1 and PAK infected with Pf4 or Pf1, respectively)
Summary
The airways of people with cystic fibrosis (CF) are persistently colonized by various opportunistic pathogens, the most prevalent being Pseudomonas aeruginosa (Pa) [1] and Aspergillus fumigatus (Af) [2]. When bacteria and fungi form biofilms, they become inherently tolerant to antibiotics [8]. With the increasing prevalence of antibiotic resistant microorganisms, alternative strategies for controlling microbial infections have become a priority. One such strategy involves the use of viruses that infect and kill bacteria or fungi. Some bacteriophage that infect Pa can promote bacterial phenotypes associated with infection. When grown as a biofilm, Pa produces abundant filamentous Pf bacteriophage (Pf phage)—often greater than 1010 plaque forming units/ml [11,12,13]. Pf phage are capable of physically trapping bacteria in the lung, producing a non-invasive infection phenotype [14], a hallmark of most chronic infections
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