Immunological blocking of spermidine-mediated host-pathogen communication provides effective control against Pseudomonas aeruginosa infection.,Microbial Biotechnology

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Immunological blocking of spermidine-mediated host-pathogen communication provides effective control against Pseudomonas aeruginosa infection.
Microbial Biotechnology ( IF 4.8 ) Pub Date : 2018-05-14 , DOI: 10.1111/1751-7915.13279
Jianhe Wang _{1,

2} , Jing Wang ₂ , Lian-Hui Zhang _{1,

2}

Affiliation

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.

中文翻译：

免疫阻断亚精胺介导的宿主-病原体交流提供了有效的控制，以抵抗铜绿假单胞菌感染。

众所周知，铜绿假单胞菌会导致威胁生命的感染。先前的研究表明，这种病原体的III型分泌系统（T3SS）是关键的毒力决定因素，它被来自哺乳动物宿主的多胺信号亚精胺（Spd）和亚精胺（Spm）激活。为了测试在疾病控制中阻断宿主与病原体交流的潜力，在这项研究中，我们使用Spm蛋白偶联物作为免疫原，开发了高效能的小鼠单克隆抗体（Mab 4E4，IgG1亚型）。抗体特异性分析表明该抗体特异性识别Spd和Spm。体外研究显示该抗体显着保护A549细胞抵抗铜绿假单胞菌感染，并通过阻止多胺摄取和下调T3SS表达来实现这种保护。小鼠体内单次注射Mab 4E4可以大大降低血清多胺水平，该水平可以维持1周以上。在铜绿假单胞菌急性感染的小鼠模型中，Mab 4E4的注射可保护小鼠免受肺损伤，并显着提高小鼠的存活率。

更新日期：2018-05-14

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