Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection

Summary Pseudomonas aeruginosa is known to cause life‐threatening infections. The previous studies showed that the type III secretion system (T3SS) of this pathogen is a key virulence determinant, which is activated by polyamines signals spermidine (Spd) and spermine (Spm) from mammalian host. To te...

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Main Authors: Jianhe Wang, Jing Wang, Lian‐Hui Zhang
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Microbial Biotechnology
Online Access:https://doi.org/10.1111/1751-7915.13279
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spelling doaj-f2a64be4d692495ca4dc79c519677e7c2020-11-25T02:49:31ZengWileyMicrobial Biotechnology1751-79152020-01-01131879610.1111/1751-7915.13279Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infectionJianhe Wang0Jing Wang1Lian‐Hui Zhang2Guangdong Province Key Laboratory of Microbial Signals and Disease Control State Key Laboratory for Conservation and Utilization of Subtropical Agro‐Bioresources College of Agriculture South China Agricultural University Guangzhou 510642 ChinaInstitute of Molecular and Cell Biology 61 Biopolis Drive Singapore 138673 SingaporeGuangdong Province Key Laboratory of Microbial Signals and Disease Control State Key Laboratory for Conservation and Utilization of Subtropical Agro‐Bioresources College of Agriculture South China Agricultural University Guangzhou 510642 ChinaSummary Pseudomonas aeruginosa is known to cause life‐threatening infections. The previous studies showed that the type III secretion system (T3SS) of this pathogen is a key virulence determinant, which is activated by polyamines signals spermidine (Spd) and spermine (Spm) from mammalian host. To test the potential of blocking host–pathogen communication in disease control, in this study we developed a high potency mouse monoclonal antibody (Mab 4E4, IgG1 sub‐isotype) by using Spm–protein conjugate as an immunogen. Antibody specificity analysis showed that the antibody specifically recognize Spd and Spm. In vitro study showed the antibody significantly protected A549 cells against P. aeruginosa infection, and this protection was achieved by blocking polyamine uptake and downregulating T3SS expression. In vivo single injection of mouse with Mab 4E4 drastically reduced the serum polyamine level, which was maintained for more than 1 week. In a murine model of P. aeruginosa acute infection, injection of Mab 4E4 protected mice from lung injury and significantly improved the survival rate of mice.https://doi.org/10.1111/1751-7915.13279
collection DOAJ
language English
format Article
sources DOAJ
author Jianhe Wang
Jing Wang
Lian‐Hui Zhang
spellingShingle Jianhe Wang
Jing Wang
Lian‐Hui Zhang
Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
Microbial Biotechnology
author_facet Jianhe Wang
Jing Wang
Lian‐Hui Zhang
author_sort Jianhe Wang
title Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
title_short Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
title_full Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
title_fullStr Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
title_full_unstemmed Immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against Pseudomonas aeruginosa infection
title_sort immunological blocking of spermidine‐mediated host–pathogen communication provides effective control against pseudomonas aeruginosa infection
publisher Wiley
series Microbial Biotechnology
issn 1751-7915
publishDate 2020-01-01
description Summary Pseudomonas aeruginosa is known to cause life‐threatening infections. The previous studies showed that the type III secretion system (T3SS) of this pathogen is a key virulence determinant, which is activated by polyamines signals spermidine (Spd) and spermine (Spm) from mammalian host. To test the potential of blocking host–pathogen communication in disease control, in this study we developed a high potency mouse monoclonal antibody (Mab 4E4, IgG1 sub‐isotype) by using Spm–protein conjugate as an immunogen. Antibody specificity analysis showed that the antibody specifically recognize Spd and Spm. In vitro study showed the antibody significantly protected A549 cells against P. aeruginosa infection, and this protection was achieved by blocking polyamine uptake and downregulating T3SS expression. In vivo single injection of mouse with Mab 4E4 drastically reduced the serum polyamine level, which was maintained for more than 1 week. In a murine model of P. aeruginosa acute infection, injection of Mab 4E4 protected mice from lung injury and significantly improved the survival rate of mice.
url https://doi.org/10.1111/1751-7915.13279
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AT lianhuizhang immunologicalblockingofspermidinemediatedhostpathogencommunicationprovideseffectivecontrolagainstpseudomonasaeruginosainfection
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