Abstract
The emergence of multi-drug resistant Pseudomonas aeruginosa necessitates the search for treatment options other than antibiotic use. The use of bacteriophages is currently being considered as an alternative to antibiotics for the treatment of bacterial infections. A number of bacteriophages were introduced to treat pneumonia in past reports. However, there are still lack of knowledge regarding the dosages, application time, mechanism and safety of phage therapy against P. aeruginosa pneumonia. We used the bacteriophage KPP10 against P. aeruginosa strain D4-induced pneumonia mouse models and observed their outcomes in comparison to control models. We found that the nasal inhalation of highly concentrated KPP10 (MOI = 80) significantly improved survival rate in pneumonia models (P < 0.01). The number of viable bacteria in both lungs and in serum were significantly decreased (P < 0.01) in phage-treated mice in comparison to the control mice. Pathological examination showed that phage-treated group had significantly reduced bleeding, inflammatory cell infiltration, and mucus secretion in lung interstitium. We also measured inflammatory cytokine levels in the serum and lung homogenates of mice. In phage-treated models, serum TNFα, IL-1β, and IFN-γ levels were significantly lower (P < 0.05, P < 0.01, and P < 0.05, respectively) than those in the control models. In the lung homogenate, the mean IL-1β level in phage-treated models was significantly lower (P < 0.05) than that of the control group. We confirmed the presence of phage in blood and lungs, and evaluated the safety of bacteriophage use in living models since bacteriophage mediated bacterial lysis arise concern of endotoxic shock. The study results suggest that phage therapy can potentially be used in treating lung infections caused by Pseudomonas aeruginosa.
Highlights
Pseudomonas aeruginosa is a gram-negative opportunistic pathogen and is one of the main pathogens that cause nosocomial infections
In terms of the need for new antibiotics due to increase in antibiotic resistance, the World Health Organization has classified P. aeruginosa under Priority 1 (Critical), which means that the establishment of phage therapy as a treatment modality that can replace antibiotic therapy is urgent [Viertel et al, 2014; World Health Organization (WHO), 2013]
We showed that phage therapy is comparable with antimicrobial therapy for treating P. aeruginosa pneumonia
Summary
Pseudomonas aeruginosa is a gram-negative opportunistic pathogen and is one of the main pathogens that cause nosocomial infections. It is a common etiology for infections in immunocompromised patients (Parker et al, 2008; Gellatly and Hancock, 2013) and in respiratoryassociated pneumonia in ICU settings. Phage Therapy in Bacterial Pneumonia and Sepsis in Pseudomonas infections; due to the emergence of multi-drug resistant P. aeruginosa, there have been cases wherein antibiotics have failed (Nathwani et al, 2014; Jernigan et al, 2020). Due to the emergence of multi-drug resistant bacteria, phage therapy has attracted widespread attention due to its possession of a completely different mechanism of action compared to antibiotic therapy (Viertel et al, 2014)
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