title: In Vivo Application of Bacteriophage as a Potential Therapeutic Agent To Control OXA-66-Like Carbapenemase-Producing Acinetobacter baumannii Strains Belonging to Sequence Type 357.
abstract: The increasing prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) strains in intensive care units has caused major problems in public health worldwide. Our aim was to determine whether this phage could be used as an alternative therapeutic agent against multidrug-resistant bacterial strains, specifically CRAB clinical isolates, using a mouse model. Ten bacteriophages that caused lysis in CRAB strains, including blaOXA-66-like genes, were isolated. YMC13/01/C62 ABA BP (phage Bϕ-C62), which showed the strongest lysis activity, was chosen for further study by transmission electron microscopy (TEM), host range test, one-step growth and phage adsorption rate, thermal and pH stability, bacteriolytic activity test, genome sequencing and bioinformatics analysis, and therapeutic effect of phage using a mouse intranasal infection model. The phage Bϕ-C62 displayed high stability at various temperatures and pH values and strong cell lysis activity in vitro The phage Bϕ-C62 genome has a double-stranded linear DNA with a length of 44,844 bp, and known virulence genes were not identified in silico. In vivo study showed that all mice treated with phage Bϕ-C62 survived after intranasal bacterial challenge. Bacterial clearance in the lung was observed within 3 days after bacterial challenge, and histologic damage also improved significantly; moreover, no side effects were observed.
  
  
  
  In our study, the novel A. baumannii phage Bϕ-C62 was characterized and evaluated in vitro, in silico, and in vivo These results, including strong lytic activities and the improvement of survival rates, showed the therapeutic potential of the phage Bϕ-C62 as an antimicrobial agent. This study reports the potential of a novel phage as a therapeutic candidate or nontoxic disinfectant against CRAB clinical isolates in vitro and in vivo.
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jongsoo
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Super-Bacteria Research Center, KRIBB, Daejeon, Republic of Korea.|Biosystems and Bioengineering Program, School of Science, University of Science and Technology (UST), Daejeon, Republic of Korea.
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Ryu
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwang-ju, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwang-ju, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea deyong@yuhs.ac.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000151:Acinetobacter Infections / Q000628:therapy*; D040981:Acinetobacter baumannii / Q000145:classification / Q000201:enzymology* / Q000254:growth & development / Q000821:virology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001435:Bacteriophages / Q000254:growth & development* / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure; D019295:Computational Biology; D004195:Disease Models, Animal; D016679:Genome, Viral; D005838:Genotype; D058507:Host Specificity; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D058885:Multilocus Sequence Typing; D000071059:Phage Therapy / Q000379:methods*; D018410:Pneumonia, Bacterial / Q000628:therapy*; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014771:Virion / Q000648:ultrastructure; D053585:Virus Attachment; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase