Investigation of PhiKZ phage therapy against Pseudomonas aeruginosa in mouse pneumonia model

Authors: KÜBRA CAN, UĞUR AKSU, OSMAN ŞADİ YENEN

Abstract: Background/aim: The aim of this study was to investigate the effects of PhiKZ phage therapy and meropenem alone or combined treatments in a pneumonia mouse model induced by the Pseudomonas aeruginosa PAO1 strain. The cross-talk between lungs and kidneys was also determined. Materials and methods: The systemic, lung-specific, and kidney-specific inflammation levels and the bacterial load in lung tissue and biochemical parameters were investigated after PhiKZ phage therapy and meropenem alone or combined treatments in a pneumonia mouse model induced by the P. aeruginosa PAO1 strain. The cross-talk between lungs and kidneys was also determined by measuring plasma levels of glycocalyx components. Results: The greatest reduction in lung bacterial load was obtained with the combined use of the PhiKZ phage and meropenem. The C-reactive protein level in the patient group was significantly higher than in the treatment groups and decreased after treatment. Serum interleukin IL-6 levels were statistically significantly higher than in the phage serum and phage + meropenem groups. Pulmonary infection can trigger proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß. Increased cytokines trigger insulin resistance in the liver. Lung infection triggers liver inflammation because there is communication between the lungs and liver. Conclusion: Elevated proinflammatory cytokines due to infection were decreased because of the reduced burden of bacterial load after treatment. This study might have proved communication between lungs and kidneys related to proinflammatory cytokines.

Keywords: Phage therapy, bacterial load, Pseudomonas aeruginosa PAO1, PhiKZ phage, pneumonia, mice model

Full Text: PDF