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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Online Access: | https://doi.org/10.1111/1751-7915.13279 |
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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 |
work_keys_str_mv |
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1724742981872779264 |