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PMCNA_RS00975 通过 TLR2 激活 NF-κB 和 ERK1/2,并有助于 的毒力。

PMCNA_RS00975 activates NF-κB and ERK1/2 through TLR2 and contributes to the virulence of .

机构信息

Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

出版信息

Front Cell Infect Microbiol. 2024 Oct 15;14:1469304. doi: 10.3389/fcimb.2024.1469304. eCollection 2024.

DOI:10.3389/fcimb.2024.1469304
PMID:39473924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11518796/
Abstract

INTRODUCTION

is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of . Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.

METHODS

In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain of , was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a gene mutant of strain was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within The recombinant protein PMCNA_RS00975 of was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.

RESULTS

The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages.

DISCUSSION

This study identified a novel virulence factor in the strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against

摘要

简介

是一种已知可引起家禽出血性败血症和肺炎的病原菌。有报道称,某些直接参与或调节铁代谢的蛋白质是 的重要毒力因子。因此,了解毒力因子并分析促炎细胞因子的作用可以帮助我们阐明潜在的发病机制。

方法

在本研究中,我们研究了编码自致病性菌株 特定噬菌体岛基因的 PMCNA_RS00975 蛋白,这是一种假定的包裹蛋白。为了进一步探讨 PMCNA_RS00975 蛋白对致病性的影响,我们使用正选择技术构建了 菌株的 基因缺失突变体。通过亚细胞定位来确定 PMCNA_RS00975 蛋白在 中的位置。可溶性表达重组蛋白 PMCNA_RS00975,并研究其在促炎细胞因子中的作用。

结果

突变体在小鼠模型中表现出明显降低的致病性。此外,亚细胞定位表明,在感染 时,PMCNA_RS00975 蛋白位于外膜上并表达。此外,我们的实验表明,重组 PMCNA_RS00975 蛋白通过 TLR2 受体触发的 NF-κB 和 ERK1/2 信号通路促进巨噬细胞中 IL-6 促炎细胞因子的分泌。

讨论

本研究鉴定了 菌株中的一种新的毒力因子,为了解发病机制和开发针对 的减毒疫苗提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/7aff8ab1da5d/fcimb-14-1469304-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/135b7c0ffb6d/fcimb-14-1469304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/71558c51d2b4/fcimb-14-1469304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/8b46ff038fd0/fcimb-14-1469304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/c3561c23aa98/fcimb-14-1469304-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/7aff8ab1da5d/fcimb-14-1469304-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/135b7c0ffb6d/fcimb-14-1469304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/71558c51d2b4/fcimb-14-1469304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/8b46ff038fd0/fcimb-14-1469304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/c3561c23aa98/fcimb-14-1469304-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600f/11518796/7aff8ab1da5d/fcimb-14-1469304-g005.jpg

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