Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice
The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to most or all available antibiotics is a global concern. Current treatments for infections caused by this bacterium have become less effective, and the need to explore new alternative therapies is urgent. Depolym...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.01407/full |
| _version_ | 1819182063717187584 |
|---|---|
| author | Can Wang Puyuan Li Yang Zhu Yong Huang Mingming Gao Xin Yuan Wenkai Niu Huiying Liu Hang Fan Yanhong Qin Yigang Tong Zhiqiang Mi Changqing Bai Changqing Bai |
| author_facet | Can Wang Puyuan Li Yang Zhu Yong Huang Mingming Gao Xin Yuan Wenkai Niu Huiying Liu Hang Fan Yanhong Qin Yigang Tong Zhiqiang Mi Changqing Bai Changqing Bai |
| author_sort | Can Wang |
| collection | DOAJ |
| description | The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to most or all available antibiotics is a global concern. Current treatments for infections caused by this bacterium have become less effective, and the need to explore new alternative therapies is urgent. Depolymerases derived from phages are emerging as attractive anti-virulence agents. In this study, a previously isolated A. baumannii phage (designated as vB_AbaM_IME285) was characterized, and genomic study was carried out using various bioinformatics tools. A gene predicted as encoding for the depolymerase was cloned and expressed, and the depolymerase activity of the recombinant enzyme (Dp49) was identified both in vitro and in experimental mice. The results showed that phage IME285 formed translucent halos around the plaques when inoculated onto a lawn of the host bacteria, exibiting depolymerase activity against this strain. On the basis of complete genome sequencing and bioinformatics analysis, ORF49 was speculated to be a gene encoding for the putative capsule depolymerase. The expressed recombinant Dp49 displayed an effective depolymerase activity and had a spectrum of activity similar to its parental phage IME285, which was active against 25 out of 49 A. baumannii strains. It was found that Dp49 greatly improved the inhibitory effect of serum on bacterial growth in vitro, and the administration of this enzyme significantly increased the survival rates of A. baumannii-infected mice in the animal experiment. In conclusion, the phage-encoded depolymerase Dp49 might be a promising alternative means of controlling infections mediated by multidrug-resistant A. baumannii. |
| first_indexed | 2024-12-22T22:40:11Z |
| format | Article |
| id | doaj.art-5d244ae5b2ba481c9c716f2e79c551f9 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T22:40:11Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5d244ae5b2ba481c9c716f2e79c551f92022-12-21T18:10:12ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-07-011110.3389/fmicb.2020.01407513074Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in MiceCan Wang0Puyuan Li1Yang Zhu2Yong Huang3Mingming Gao4Xin Yuan5Wenkai Niu6Huiying Liu7Hang Fan8Yanhong Qin9Yigang Tong10Zhiqiang Mi11Changqing Bai12Changqing Bai13Department of Respiratory Medicine, Fuyang Hospital of Anhui Medical University, Anhui, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Respiratory Medicine, Fuyang Hospital of Anhui Medical University, Anhui, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Respiratory and Critical Care Diseases, General Hospital of Shenzhen University, Shenzhen, ChinaThe rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to most or all available antibiotics is a global concern. Current treatments for infections caused by this bacterium have become less effective, and the need to explore new alternative therapies is urgent. Depolymerases derived from phages are emerging as attractive anti-virulence agents. In this study, a previously isolated A. baumannii phage (designated as vB_AbaM_IME285) was characterized, and genomic study was carried out using various bioinformatics tools. A gene predicted as encoding for the depolymerase was cloned and expressed, and the depolymerase activity of the recombinant enzyme (Dp49) was identified both in vitro and in experimental mice. The results showed that phage IME285 formed translucent halos around the plaques when inoculated onto a lawn of the host bacteria, exibiting depolymerase activity against this strain. On the basis of complete genome sequencing and bioinformatics analysis, ORF49 was speculated to be a gene encoding for the putative capsule depolymerase. The expressed recombinant Dp49 displayed an effective depolymerase activity and had a spectrum of activity similar to its parental phage IME285, which was active against 25 out of 49 A. baumannii strains. It was found that Dp49 greatly improved the inhibitory effect of serum on bacterial growth in vitro, and the administration of this enzyme significantly increased the survival rates of A. baumannii-infected mice in the animal experiment. In conclusion, the phage-encoded depolymerase Dp49 might be a promising alternative means of controlling infections mediated by multidrug-resistant A. baumannii.https://www.frontiersin.org/article/10.3389/fmicb.2020.01407/fulldepolymerasephage-derivedAcinetobacter baumanniiidentificationtherapeutic application |
| spellingShingle | Can Wang Puyuan Li Yang Zhu Yong Huang Mingming Gao Xin Yuan Wenkai Niu Huiying Liu Hang Fan Yanhong Qin Yigang Tong Zhiqiang Mi Changqing Bai Changqing Bai Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice Frontiers in Microbiology depolymerase phage-derived Acinetobacter baumannii identification therapeutic application |
| title | Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice |
| title_full | Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice |
| title_fullStr | Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice |
| title_full_unstemmed | Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice |
| title_short | Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice |
| title_sort | identification of a novel acinetobacter baumannii phage derived depolymerase and its therapeutic application in mice |
| topic | depolymerase phage-derived Acinetobacter baumannii identification therapeutic application |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.01407/full |
| work_keys_str_mv | AT canwang identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT puyuanli identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT yangzhu identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT yonghuang identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT mingminggao identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT xinyuan identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT wenkainiu identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT huiyingliu identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT hangfan identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT yanhongqin identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT yigangtong identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT zhiqiangmi identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT changqingbai identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice AT changqingbai identificationofanovelacinetobacterbaumanniiphagederiveddepolymeraseanditstherapeuticapplicationinmice |