Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo
Acinetobacter baumannii is emerging as a challenging nosocomial pathogen due to its rapid evolution of antibiotic resistance. We report characterization of two novel bacteriophages, PBAB08 and PBAB25, infecting clinically isolated, multidrug-resistant (MDR) A. baumannii strains. Both phages belonged...
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| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00696/full |
| _version_ | 1819207982381006848 |
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| author | Kyoungeun Cha Kyoungeun Cha Hynu K. Oh Jae Y. Jang Yunyeol Jo Won K. Kim Geon U. Ha Kwan S. Ko Heejoon Myung Heejoon Myung |
| author_facet | Kyoungeun Cha Kyoungeun Cha Hynu K. Oh Jae Y. Jang Yunyeol Jo Won K. Kim Geon U. Ha Kwan S. Ko Heejoon Myung Heejoon Myung |
| author_sort | Kyoungeun Cha |
| collection | DOAJ |
| description | Acinetobacter baumannii is emerging as a challenging nosocomial pathogen due to its rapid evolution of antibiotic resistance. We report characterization of two novel bacteriophages, PBAB08 and PBAB25, infecting clinically isolated, multidrug-resistant (MDR) A. baumannii strains. Both phages belonged to Myoviridae of Caudovirales as their morphology observed under an electron microscope. Their genomes were double stranded linear DNAs of 42,312 base pairs and 40,260 base pairs, respectively. The two phages were distinct from known Acinetobacter phages when whole genome sequences were compared. PBAB08 showed a 99% similarity with 57% sequence coverage to phage AB1 and PBAB25 showed a 97% similarity with 78% sequence coverage to phage IME_AB3. BLASTN significant alignment coverage of all other known phages were <30%. Seventy six and seventy genes encoding putative phage proteins were found in the genomes of PBAB08 and PBAB25, respectively. Their genomic organizations and sequence similarities were consistent with the modular theory of phage evolution. Therapeutic efficacy of a phage cocktail containing the two and other phages were evaluated in a mice model with nasal infection of MDR A. baumannii. Mice treated with the phage cocktail showed a 2.3-fold higher survival rate than those untreated in 7 days post infection. In addition, 1/100 reduction of the number of A. baumannii in the lung of the mice treated with the phage cocktail was observed. Also, inflammatory responses of mice which were injected with the phage cocktail by intraperitoneal, intranasal, or oral route was investigated. Increase in serum cytokine was minimal regardless of the injection route. A 20% increase in IgE production was seen in intraperitoneal injection route, but not in other routes. Thus, the cocktail containing the two newly isolated phages could serve as a potential candidate for therapeutic interventions to treat A. baummannii infections. |
| first_indexed | 2024-12-23T05:32:08Z |
| format | Article |
| id | doaj.art-5118a7756ae24bedb3ef6c11caa89875 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-23T05:32:08Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5118a7756ae24bedb3ef6c11caa898752022-12-21T17:58:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-04-01910.3389/fmicb.2018.00696324473Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in VivoKyoungeun Cha0Kyoungeun Cha1Hynu K. Oh2Jae Y. Jang3Yunyeol Jo4Won K. Kim5Geon U. Ha6Kwan S. Ko7Heejoon Myung8Heejoon Myung9Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaThe Bacteriophage Bank of Korea, Hankuk University of Foreign Studies, Yong-In, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaSamsung Medical Center, Sungkyukwan University School of Medicine, Suwon, South KoreaDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, South KoreaThe Bacteriophage Bank of Korea, Hankuk University of Foreign Studies, Yong-In, South KoreaAcinetobacter baumannii is emerging as a challenging nosocomial pathogen due to its rapid evolution of antibiotic resistance. We report characterization of two novel bacteriophages, PBAB08 and PBAB25, infecting clinically isolated, multidrug-resistant (MDR) A. baumannii strains. Both phages belonged to Myoviridae of Caudovirales as their morphology observed under an electron microscope. Their genomes were double stranded linear DNAs of 42,312 base pairs and 40,260 base pairs, respectively. The two phages were distinct from known Acinetobacter phages when whole genome sequences were compared. PBAB08 showed a 99% similarity with 57% sequence coverage to phage AB1 and PBAB25 showed a 97% similarity with 78% sequence coverage to phage IME_AB3. BLASTN significant alignment coverage of all other known phages were <30%. Seventy six and seventy genes encoding putative phage proteins were found in the genomes of PBAB08 and PBAB25, respectively. Their genomic organizations and sequence similarities were consistent with the modular theory of phage evolution. Therapeutic efficacy of a phage cocktail containing the two and other phages were evaluated in a mice model with nasal infection of MDR A. baumannii. Mice treated with the phage cocktail showed a 2.3-fold higher survival rate than those untreated in 7 days post infection. In addition, 1/100 reduction of the number of A. baumannii in the lung of the mice treated with the phage cocktail was observed. Also, inflammatory responses of mice which were injected with the phage cocktail by intraperitoneal, intranasal, or oral route was investigated. Increase in serum cytokine was minimal regardless of the injection route. A 20% increase in IgE production was seen in intraperitoneal injection route, but not in other routes. Thus, the cocktail containing the two newly isolated phages could serve as a potential candidate for therapeutic interventions to treat A. baummannii infections.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00696/fullmultidrug-resistanceAcinetobacter baumanniibacteriophage therapymouse modelgenome analysis |
| spellingShingle | Kyoungeun Cha Kyoungeun Cha Hynu K. Oh Jae Y. Jang Yunyeol Jo Won K. Kim Geon U. Ha Kwan S. Ko Heejoon Myung Heejoon Myung Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo Frontiers in Microbiology multidrug-resistance Acinetobacter baumannii bacteriophage therapy mouse model genome analysis |
| title | Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo |
| title_full | Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo |
| title_fullStr | Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo |
| title_full_unstemmed | Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo |
| title_short | Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo |
| title_sort | characterization of two novel bacteriophages infecting multidrug resistant mdr acinetobacter baumannii and evaluation of their therapeutic efficacy in vivo |
| topic | multidrug-resistance Acinetobacter baumannii bacteriophage therapy mouse model genome analysis |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00696/full |
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