Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge t...

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Main Authors: Zijing Wang, Ruopeng Cai, Gang Wang, Zhimin Guo, Xiao Liu, Yuan Guan, Yalu Ji, Hao Zhang, Hengyu Xi, Rihong Zhao, Lanting Bi, Shanshan Liu, Li Yang, Xin Feng, Changjiang Sun, Liancheng Lei, Wenyu Han, Jingmin Gu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.674068/full
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author Zijing Wang
Ruopeng Cai
Gang Wang
Zhimin Guo
Xiao Liu
Yuan Guan
Yalu Ji
Hao Zhang
Hengyu Xi
Rihong Zhao
Lanting Bi
Shanshan Liu
Li Yang
Xin Feng
Changjiang Sun
Liancheng Lei
Wenyu Han
Wenyu Han
Jingmin Gu
Jingmin Gu
author_facet Zijing Wang
Ruopeng Cai
Gang Wang
Zhimin Guo
Xiao Liu
Yuan Guan
Yalu Ji
Hao Zhang
Hengyu Xi
Rihong Zhao
Lanting Bi
Shanshan Liu
Li Yang
Xin Feng
Changjiang Sun
Liancheng Lei
Wenyu Han
Wenyu Han
Jingmin Gu
Jingmin Gu
author_sort Zijing Wang
collection DOAJ
description Klebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge to the treatment of K. pneumoniae infection. In this study, a novel bacteriophage that specifically infects K. pneumoniae was isolated and named as vB_KpnM_P-KP2 (abbreviated as P-KP2). The biological characteristics of P-KP2 and the bioinformatics of its genome were analyzed, and then the therapeutic effect of P-KP2 was tested by animal experiments. P-KP2 presents high lysis efficiency in vitro. The genome of P-KP2 shows homology with nine phages which belong to “KP15 virus” family and its genome comprises 172,138 bp and 264 ORFs. Besides, P-KP2 was comparable to gentamicin in the treatment of lethal pneumonia caused by K. pneumoniae W-KP2 (K47 serotype). Furthermore, the combined treatment of P-KP2 and gentamicin completely rescued the infected mice. Therefore, this study not only introduces a new member to the phage therapeutic library, but also serves as a reference for other phage-antibiotic combinations to combat MDR pathogens.
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spelling doaj.art-3a3f0fd7fe1d4c778aabffd975998bef2022-12-21T21:56:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-04-011210.3389/fmicb.2021.674068674068Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniaeZijing Wang0Ruopeng Cai1Gang Wang2Zhimin Guo3Xiao Liu4Yuan Guan5Yalu Ji6Hao Zhang7Hengyu Xi8Rihong Zhao9Lanting Bi10Shanshan Liu11Li Yang12Xin Feng13Changjiang Sun14Liancheng Lei15Wenyu Han16Wenyu Han17Jingmin Gu18Jingmin Gu19Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Animal Science and Technology, Jilin Agricultural University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Clinical Laboratory, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Chinese Journal of Veterinary Science, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaJiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaJiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, ChinaKlebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge to the treatment of K. pneumoniae infection. In this study, a novel bacteriophage that specifically infects K. pneumoniae was isolated and named as vB_KpnM_P-KP2 (abbreviated as P-KP2). The biological characteristics of P-KP2 and the bioinformatics of its genome were analyzed, and then the therapeutic effect of P-KP2 was tested by animal experiments. P-KP2 presents high lysis efficiency in vitro. The genome of P-KP2 shows homology with nine phages which belong to “KP15 virus” family and its genome comprises 172,138 bp and 264 ORFs. Besides, P-KP2 was comparable to gentamicin in the treatment of lethal pneumonia caused by K. pneumoniae W-KP2 (K47 serotype). Furthermore, the combined treatment of P-KP2 and gentamicin completely rescued the infected mice. Therefore, this study not only introduces a new member to the phage therapeutic library, but also serves as a reference for other phage-antibiotic combinations to combat MDR pathogens.https://www.frontiersin.org/articles/10.3389/fmicb.2021.674068/fullbacteriophageKlebsiella pneumoniaegenome sequencingbioinformatics analysisphage therapy
spellingShingle Zijing Wang
Ruopeng Cai
Gang Wang
Zhimin Guo
Xiao Liu
Yuan Guan
Yalu Ji
Hao Zhang
Hengyu Xi
Rihong Zhao
Lanting Bi
Shanshan Liu
Li Yang
Xin Feng
Changjiang Sun
Liancheng Lei
Wenyu Han
Wenyu Han
Jingmin Gu
Jingmin Gu
Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
Frontiers in Microbiology
bacteriophage
Klebsiella pneumoniae
genome sequencing
bioinformatics analysis
phage therapy
title Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
title_full Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
title_fullStr Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
title_full_unstemmed Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
title_short Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae
title_sort combination therapy of phage vb kpnm p kp2 and gentamicin combats acute pneumonia caused by k47 serotype klebsiella pneumoniae
topic bacteriophage
Klebsiella pneumoniae
genome sequencing
bioinformatics analysis
phage therapy
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.674068/full
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