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

Jongsoo Jeon, Choong Min Ryu, Jun Young Lee, Jong Hwan Park, Dongeun Yong, Kyungwon Lee

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4200-4208
Number of pages9
JournalApplied and Environmental Microbiology
Volume82
Issue number14
DOIs
Publication statusPublished - 2016

Bibliographical note

Funding Information:
This work, including the efforts of Dongeun Yong, was funded by National Research Foundation of Korea (NRF) (2012R1A1A2009064). This work, including the efforts of Dongeun Yong, was funded by Ministry of Science, ICT and Future Planning (MSIP) (2014M3A6B2060509).

Publisher Copyright:
© 2016, American Society for Microbiology.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

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