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Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type Acinetobacter baumannii
Alexander I Borzilov1, Nikolay V Volozhantsev1, Olga V Korobova1
1State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia.
Abstract:
Acinetobacter baumannii is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn skin infection models. In the mouse sepsis model, in the case of prevention or early treatment, a single K9-specific phage or recombinant depolymerase injection was able to protect 100% of the mice after parenteral infection with a lethal dose of A. baumannii of the K9-type, with complete eradication of the pathogen. In the case of delayed treatment, mouse survival decreased to 70% when injected with the phage and to 40% when treated with the recombinant enzyme. In the mouse burn skin infection model, the number of A. baumannii cells on the surface of the wound and in the deep layers of the skin decreased by several-fold after treatment with both the K9-specific phage and the recombinant depolymerase. The phage and recombinant depolymerase were highly stable and retained activity under a wide range of temperatures and pH values. The results obtained contribute to expanding our understanding of the in vivo therapeutic potential of specific phages and phage-derived depolymerases interacting with A. baumannii of different capsular types.
Insights
A K9-specific phage and its depolymerase show significant therapeutic potential against Acinetobacter baumannii infections in mice, eradicating the pathogen in sepsis models and reducing bacterial load in skin infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriology
Background:
- Acinetobacter baumannii is a significant nosocomial pathogen causing severe infections, especially in vulnerable populations.
- The emergence of antibiotic resistance necessitates novel therapeutic strategies against A. baumannii.
Purpose of the Study:
- To evaluate the in vivo therapeutic efficacy of the K9-specific virulent phage AM24 and its encoded depolymerase, DepAPK09.
- To assess the stability and activity range of the phage and depolymerase under various conditions.
Main Methods:
- In vivo mouse models were utilized, including sepsis and burn skin infection models.
- Phage AM24 and recombinant DepAPK09 were administered for prevention, early treatment, and delayed treatment in sepsis models.
- Bacterial load reduction was quantified in skin infection models.
- Stability assays were performed across a range of temperatures and pH values.
Main Results:
- A single administration of phage AM24 or DepAPK09 provided 100% protection in the mouse sepsis model when used for prevention or early treatment.
- Delayed treatment with phage AM24 resulted in 70% survival, while DepAPK09 yielded 40% survival.
- Both phage and depolymerase significantly reduced A. baumannii counts in burn wound skin infections.
- The phage and depolymerase demonstrated high stability across diverse temperatures and pH levels.
Conclusions:
- K9-specific phage AM24 and its depolymerase DepAPK09 exhibit potent in vivo therapeutic activity against A. baumannii.
- These findings support the potential of phage therapy and depolymerases as alternative treatments for A. baumannii infections.
- The stability of these agents suggests their suitability for a broad range of clinical applications.
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