Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type <i>Acinetobacter baumannii</i> in Mouse Sepsis and Burn Skin Infection Models
Alexander I. Borzilov,
Nikolay V. Volozhantsev,
Olga V. Korobova,
Lyubov V. Kolupaeva,
Evgenia S. Pereskokova,
Tatiana I. Kombarova,
Mikhail M. Shneider,
Konstantin A. Miroshnikov,
Ivan A. Dyatlov,
Anastasia V. Popova
Affiliations
Alexander I. Borzilov
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Nikolay V. Volozhantsev
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Olga V. Korobova
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Lyubov V. Kolupaeva
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Evgenia S. Pereskokova
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Tatiana I. Kombarova
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Mikhail M. Shneider
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Konstantin A. Miroshnikov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Ivan A. Dyatlov
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
Anastasia V. Popova
State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia
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.