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The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections

The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study...

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Autores principales: Liu, Yannan, Leung, Sharon Shui Yee, Guo, Yatao, Zhao, Lili, Jiang, Ning, Mi, Liyuan, Li, Puyuan, Wang, Can, Qin, Yanhong, Mi, Zhiqiang, Bai, Changqing, Gao, Zhancheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431613/
https://www.ncbi.nlm.nih.gov/pubmed/30936862
http://dx.doi.org/10.3389/fmicb.2019.00545
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author Liu, Yannan
Leung, Sharon Shui Yee
Guo, Yatao
Zhao, Lili
Jiang, Ning
Mi, Liyuan
Li, Puyuan
Wang, Can
Qin, Yanhong
Mi, Zhiqiang
Bai, Changqing
Gao, Zhancheng
author_facet Liu, Yannan
Leung, Sharon Shui Yee
Guo, Yatao
Zhao, Lili
Jiang, Ning
Mi, Liyuan
Li, Puyuan
Wang, Can
Qin, Yanhong
Mi, Zhiqiang
Bai, Changqing
Gao, Zhancheng
author_sort Liu, Yannan
collection PubMed
description The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study, we found that a capsule depolymerase Dpo48 could strip bacterial capsules, and the non-capsuled A. baumannii were significantly decreased in the presence of serum complement in vitro. Here, we further explored its potential as a therapeutic agent for controlling systemic infections caused by extensively drug-resistant A. baumannii. Prior to mammalian studies, the anti-virulence efficacy of Dpo48 was first tested in a Galleria mellonella infection model. Survival rate of Dpo48-pretreated bacteria or Dpo48 treatment group was significantly increased compared to the infective G. mellonella without treatment. Furthermore, the safety and therapeutic efficacy of Dpo48 to mice were evaluated. The mice treated with Dpo48 displayed normal serum levels of TBIL, AST, ALT, ALP, Cr, BUN and LDH, while no significant histopathology changes were observed in tissues of liver, spleen, lung, and kidney. Treatment with Dpo48 could rescue normal and immunocompromised mice from lethal peritoneal sepsis, with the bacterial counts in blood, liver, spleen, lung, and kidney significantly reduced by 1.4–3.3 log colony-forming units at 4 h posttreatment. Besides, the hemolysis and cytotoxicity assays showed that Dpo48 was non-homolytic to human red blood cells and non-toxic to human lung, liver and kidney cell lines. Overall, the present study demonstrated the promising potential of capsule depolymerases as therapeutic agents to prevent antibiotic-resistant A. baumannii infections.
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spelling pubmed-64316132019-04-01 The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections Liu, Yannan Leung, Sharon Shui Yee Guo, Yatao Zhao, Lili Jiang, Ning Mi, Liyuan Li, Puyuan Wang, Can Qin, Yanhong Mi, Zhiqiang Bai, Changqing Gao, Zhancheng Front Microbiol Microbiology The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study, we found that a capsule depolymerase Dpo48 could strip bacterial capsules, and the non-capsuled A. baumannii were significantly decreased in the presence of serum complement in vitro. Here, we further explored its potential as a therapeutic agent for controlling systemic infections caused by extensively drug-resistant A. baumannii. Prior to mammalian studies, the anti-virulence efficacy of Dpo48 was first tested in a Galleria mellonella infection model. Survival rate of Dpo48-pretreated bacteria or Dpo48 treatment group was significantly increased compared to the infective G. mellonella without treatment. Furthermore, the safety and therapeutic efficacy of Dpo48 to mice were evaluated. The mice treated with Dpo48 displayed normal serum levels of TBIL, AST, ALT, ALP, Cr, BUN and LDH, while no significant histopathology changes were observed in tissues of liver, spleen, lung, and kidney. Treatment with Dpo48 could rescue normal and immunocompromised mice from lethal peritoneal sepsis, with the bacterial counts in blood, liver, spleen, lung, and kidney significantly reduced by 1.4–3.3 log colony-forming units at 4 h posttreatment. Besides, the hemolysis and cytotoxicity assays showed that Dpo48 was non-homolytic to human red blood cells and non-toxic to human lung, liver and kidney cell lines. Overall, the present study demonstrated the promising potential of capsule depolymerases as therapeutic agents to prevent antibiotic-resistant A. baumannii infections. Frontiers Media S.A. 2019-03-18 /pmc/articles/PMC6431613/ /pubmed/30936862 http://dx.doi.org/10.3389/fmicb.2019.00545 Text en Copyright © 2019 Liu, Leung, Guo, Zhao, Jiang, Mi, Li, Wang, Qin, Mi, Bai and Gao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Liu, Yannan
Leung, Sharon Shui Yee
Guo, Yatao
Zhao, Lili
Jiang, Ning
Mi, Liyuan
Li, Puyuan
Wang, Can
Qin, Yanhong
Mi, Zhiqiang
Bai, Changqing
Gao, Zhancheng
The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title_full The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title_fullStr The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title_full_unstemmed The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title_short The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections
title_sort capsule depolymerase dpo48 rescues galleria mellonella and mice from acinetobacter baumannii systemic infections
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431613/
https://www.ncbi.nlm.nih.gov/pubmed/30936862
http://dx.doi.org/10.3389/fmicb.2019.00545
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