Abstract
BackgroundAcinetobacter 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 Βϕ-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.ResultsThe A. baumannii phage Βϕ-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 Βϕ-R2096, which belongs to the Myoviridae family, was analyzed. Phage Βϕ-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 Βϕ-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 Βϕ-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.ConclusionThe results of this study strongly suggest that phage Βϕ-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.
Highlights
Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units
pulsed-field gel electrophoresis (PFGE) of 31 carbapenem-resistant and -susceptible A. baumannii strains showed different clonality with distinguishable restriction patterns (Additional file 1: Figure S1), and multilocus sequence typing (MLST) analysis of the 20 carbapenem-resistant A. baumannii (CRAB) strains, including A. baumannii YMC13/03/R2096, indicated that they were sequence type (ST) 357, which belongs to European clone II
Characterization of phage Bφ-R2096 infecting carbapenem-resistant A. baumannii strains As shown Fig. 1a, electron microscopy indicated that phage Bφ-R2096 belongs to the Myoviridae family, with
Summary
Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infection in intensive care units. Carbapenem-resistant A. baumannii (CRAB) strains have been increasing in the past decade, and they have caused major medical problems worldwide. Acinetobacter baumannii, a Gram-negative coccobacillus, is an important global nosocomial pathogen species that causes infections such as bacteremia, pneumonia, urinary tract infections, wound infections, and meningitis in critically immunocompromised patients in intensive care units (ICUs) [5]. Carbapenems have been the most effective antibiotics against the serious infections caused by Acinetobacter spp.; carbapenem resistance rates among A. baumannii isolates have increased significantly in many countries, including the USA [8], China [9], and South Korea [10, 11], since the first reported emergence in New York, USA, in 1991 [12]. The carbapenem resistance of A. baumannii isolates is mostly due to the production of OXA-type carbapenemases (class D carbapenemase-hydrolyzing oxacillinases) [19,20,21]
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