Bacteriophages isolated from mouse feces attenuates pneumonia mice caused by Pseudomonas aeruginosa
Nuttawut Sutnu1,2, Wiwat Chancharoenthana3,4, Supitcha Kamolratanakul3,4
1Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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.
Insights
Bacteriophages isolated from mouse feces effectively treated Pseudomonas aeruginosa pneumonia. Phage therapy enhanced neutrophil bacterial killing, offering a promising alternative treatment strategy.
Area of Science:
- Microbiology
- Immunology
- Bacteriophage Therapy
Background:
- Bacteriophages (phages) are typically isolated from environmental sources.
- Phages from host feces may offer greater specificity against pathogenic bacteria.
- Environmental phages might impact non-pathogenic host bacteria.
Purpose of the Study:
- To investigate the efficacy of fecal bacteriophages against Pseudomonas aeruginosa-induced pneumonia in mice.
- To evaluate different administration routes (intratracheal and intravenous) for phage therapy.
- To elucidate the mechanism of phage-mediated pneumonia attenuation.
Main Methods:
- Isolation of bacteriophages from mouse feces.
- Administration of phages via intratracheal (IT) or intravenous (IV) routes in a mouse pneumonia model.
- Assessment of pneumonia severity through mortality, cytokine levels, bacteremia, bacterial load in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs).
Main Results:
- Both IT and IV phage administration reduced pneumonia severity, including decreased mortality, serum cytokines, bacteremia, and bacterial load in BALF.
- Phage abundance in BALF was similar for both IT and IV routes, indicating flexible administration.
- Bacteriophages enhanced neutrophil bactericidal activity against P. aeruginosa in vitro, but did not significantly affect NETs formation.
Conclusions:
- Fecal bacteriophages are effective in treating P. aeruginosa pneumonia in a mouse model.
- Phage therapy attenuates pneumonia primarily by enhancing neutrophil bactericidal activity, not by inducing NETs.
- Isolating phages from infected hosts presents a practical approach for future therapeutic development.
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