Bacteriophages isolated from mouse feces attenuates pneumonia mice caused by Pseudomonas aeruginosa

Author:

Sutnu Nuttawut,Chancharoenthana WiwatORCID,Kamolratanakul Supitcha,Phuengmaung Pornpimol,Singkham-In Uthaibhorn,Chongrak Chiratchaya,Montathip Sirikan,Wannigama Dhammika LeshanORCID,Chatsuwan Tanittha,Ounjai Puey,Schultz Marcus J.,Leelahavanichkul AsadaORCID

Abstract

Background Most of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host. Methods Here, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase). Results Interestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-α, but not IL-1β. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa can be discovered from feces of the host. Conclusions The phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted.

Publisher

Public Library of Science (PLoS)

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