Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia

Jongsoo Jeon, Jong Hwan Park, Dongeun Yong

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3 Citations (Scopus)

Abstract

Background: Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units. In particular, carbapenem-resistant A. baumannii (CRAB) strains have been increasing in the past decade, and they have caused major medical problems worldwide. In this study, a novel A. baumannii lytic phage, the YMC 13/03/R2096 ABA BP (phage Β-R2096), which specifically causes the lysis of CRAB strains, was characterized in detail in vitro and in silico, and the in vivo effectiveness of phage therapy was evaluated using Galleria mellonella and a mouse model of acute pneumonia. Results: The A. baumannii phage Β-R2096 was isolated from sewage water using CRAB clinical strains selected from patients at a university hospital in South Korea. The complete genome of the phage Β-R2096, which belongs to the Myoviridae family, was analyzed. Phage Β-R2096 inhibited bacterial growth in a dose-dependent manner and exhibited high bacteriolytic activity at MOI = 10. In the evaluation of its therapeutic potential against CRAB clinical isolates using two in vivo models, phage Β-R2096 increased the survival rates of both G. mellonella larvae (from 0 to 50% at 24 h) and mice (from 30% with MOI = 0.1 to 100% with MOI = 10 for 12 days) in post-infection of CRAB. In particular, phage Β-R2096 strongly ameliorated histologic damage to infected lungs, with bacterial clearance in the lungs observed on day 3 postinfection in the mouse acute pneumonia model. Moreover, in vivo studies revealed no mortality or serious side effects in phage-treated groups. Conclusion: The results of this study strongly suggest that phage Β-R2096, a novel A. baumannii lytic phage, could be an alternative antibacterial agent to control CRAB infections. This study is the first report to compare in vivo evaluations (G. mellonella larvae and a mouse acute pneumonia model) of the therapeutic efficacy of a phage against CRAB infections.

Original languageEnglish
Article number70
JournalBMC Microbiology
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Apr 2

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Acinetobacter baumannii
Carbapenems
Bacteriophages
Larva
Pneumonia
Acinetobacter Infections
Myoviridae
Lung
Republic of Korea
Cross Infection
Sewage
Computer Simulation
Intensive Care Units
Survival Rate
Genome

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

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title = "Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia",
abstract = "Background: Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units. In particular, carbapenem-resistant A. baumannii (CRAB) strains have been increasing in the past decade, and they have caused major medical problems worldwide. In this study, a novel A. baumannii lytic phage, the YMC 13/03/R2096 ABA BP (phage Β-R2096), which specifically causes the lysis of CRAB strains, was characterized in detail in vitro and in silico, and the in vivo effectiveness of phage therapy was evaluated using Galleria mellonella and a mouse model of acute pneumonia. Results: The A. baumannii phage Β-R2096 was isolated from sewage water using CRAB clinical strains selected from patients at a university hospital in South Korea. The complete genome of the phage Β-R2096, which belongs to the Myoviridae family, was analyzed. Phage Β-R2096 inhibited bacterial growth in a dose-dependent manner and exhibited high bacteriolytic activity at MOI = 10. In the evaluation of its therapeutic potential against CRAB clinical isolates using two in vivo models, phage Β-R2096 increased the survival rates of both G. mellonella larvae (from 0 to 50{\%} at 24 h) and mice (from 30{\%} with MOI = 0.1 to 100{\%} with MOI = 10 for 12 days) in post-infection of CRAB. In particular, phage Β-R2096 strongly ameliorated histologic damage to infected lungs, with bacterial clearance in the lungs observed on day 3 postinfection in the mouse acute pneumonia model. Moreover, in vivo studies revealed no mortality or serious side effects in phage-treated groups. Conclusion: The results of this study strongly suggest that phage Β-R2096, a novel A. baumannii lytic phage, could be an alternative antibacterial agent to control CRAB infections. This study is the first report to compare in vivo evaluations (G. mellonella larvae and a mouse acute pneumonia model) of the therapeutic efficacy of a phage against CRAB infections.",
author = "Jongsoo Jeon and Park, {Jong Hwan} and Dongeun Yong",
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N2 - Background: Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units. In particular, carbapenem-resistant A. baumannii (CRAB) strains have been increasing in the past decade, and they have caused major medical problems worldwide. In this study, a novel A. baumannii lytic phage, the YMC 13/03/R2096 ABA BP (phage Β-R2096), which specifically causes the lysis of CRAB strains, was characterized in detail in vitro and in silico, and the in vivo effectiveness of phage therapy was evaluated using Galleria mellonella and a mouse model of acute pneumonia. Results: The A. baumannii phage Β-R2096 was isolated from sewage water using CRAB clinical strains selected from patients at a university hospital in South Korea. The complete genome of the phage Β-R2096, which belongs to the Myoviridae family, was analyzed. Phage Β-R2096 inhibited bacterial growth in a dose-dependent manner and exhibited high bacteriolytic activity at MOI = 10. In the evaluation of its therapeutic potential against CRAB clinical isolates using two in vivo models, phage Β-R2096 increased the survival rates of both G. mellonella larvae (from 0 to 50% at 24 h) and mice (from 30% with MOI = 0.1 to 100% with MOI = 10 for 12 days) in post-infection of CRAB. In particular, phage Β-R2096 strongly ameliorated histologic damage to infected lungs, with bacterial clearance in the lungs observed on day 3 postinfection in the mouse acute pneumonia model. Moreover, in vivo studies revealed no mortality or serious side effects in phage-treated groups. Conclusion: The results of this study strongly suggest that phage Β-R2096, a novel A. baumannii lytic phage, could be an alternative antibacterial agent to control CRAB infections. This study is the first report to compare in vivo evaluations (G. mellonella larvae and a mouse acute pneumonia model) of the therapeutic efficacy of a phage against CRAB infections.

AB - Background: Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units. In particular, carbapenem-resistant A. baumannii (CRAB) strains have been increasing in the past decade, and they have caused major medical problems worldwide. In this study, a novel A. baumannii lytic phage, the YMC 13/03/R2096 ABA BP (phage Β-R2096), which specifically causes the lysis of CRAB strains, was characterized in detail in vitro and in silico, and the in vivo effectiveness of phage therapy was evaluated using Galleria mellonella and a mouse model of acute pneumonia. Results: The A. baumannii phage Β-R2096 was isolated from sewage water using CRAB clinical strains selected from patients at a university hospital in South Korea. The complete genome of the phage Β-R2096, which belongs to the Myoviridae family, was analyzed. Phage Β-R2096 inhibited bacterial growth in a dose-dependent manner and exhibited high bacteriolytic activity at MOI = 10. In the evaluation of its therapeutic potential against CRAB clinical isolates using two in vivo models, phage Β-R2096 increased the survival rates of both G. mellonella larvae (from 0 to 50% at 24 h) and mice (from 30% with MOI = 0.1 to 100% with MOI = 10 for 12 days) in post-infection of CRAB. In particular, phage Β-R2096 strongly ameliorated histologic damage to infected lungs, with bacterial clearance in the lungs observed on day 3 postinfection in the mouse acute pneumonia model. Moreover, in vivo studies revealed no mortality or serious side effects in phage-treated groups. Conclusion: The results of this study strongly suggest that phage Β-R2096, a novel A. baumannii lytic phage, could be an alternative antibacterial agent to control CRAB infections. This study is the first report to compare in vivo evaluations (G. mellonella larvae and a mouse acute pneumonia model) of the therapeutic efficacy of a phage against CRAB infections.

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