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猪链球菌2型中II型毒素-抗毒素系统ParDE的功能分析

Functional analysis of the type II toxin-antitoxin system ParDE in Streptococcus suis serotype 2.

作者信息

Gu Qibing, Zhu Xiayu, Ma Jiale, Jiang Tao, Pan Zihao, Yao Huochun

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.

Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing, 210095, China.

出版信息

BMC Vet Res. 2025 Jan 20;21(1):30. doi: 10.1186/s12917-024-04069-w.

DOI:10.1186/s12917-024-04069-w
PMID:39833840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11744833/
Abstract

Streptococcus suis (S. suis) is a major pathogen in swine and poses a potential zoonotic threat, which may cause serious diseases. Many toxin-antitoxin (TA) systems have been discovered in S. suis, but their functions have not yet been fully elucidated. In this study, an auto-regulating type II TA system, ParDE, was identified in S. suis serotype 2 strain ZY05719. We constructed a mutant strain, ΔparDE, to explore its functions in bacterial virulence, various stress responses, and biofilm formation capabilities. The toxicity exerted by the toxin ParE can be neutralized by the antitoxin ParD. The β-galactosidase activity analysis indicated that ParDE has an autoregulatory function. An electrophoretic mobility shift assay (EMSA) confirmed that the antitoxin ParD bound to the promoter of ParDE as dimers. In the mouse infection model, the deletion of ParDE in ZY05719 significantly attenuated virulence. ΔparDE also exhibited a reduced anti-oxidative stress ability, and ΔparDE was more susceptible to phagocytosis and killing by macrophages. Moreover, the biofilm formation ability of the ΔparDE strain was significantly enhanced compared to ZY05719. Taken together, these findings indicate that the type II TA system ParDE plays a significant role in the pathogenesis of S. suis, providing new insights into its pathogenic mechanisms.

摘要

猪链球菌是猪的主要病原菌,具有潜在的人畜共患病威胁,可能引发严重疾病。在猪链球菌中已发现许多毒素-抗毒素(TA)系统,但其功能尚未完全阐明。在本研究中,在猪链球菌2型菌株ZY05719中鉴定出一种自我调节的II型TA系统ParDE。我们构建了一个突变株ΔparDE,以探究其在细菌毒力、各种应激反应和生物膜形成能力方面的功能。毒素ParE产生的毒性可被抗毒素ParD中和。β-半乳糖苷酶活性分析表明ParDE具有自我调节功能。电泳迁移率变动分析(EMSA)证实抗毒素ParD以二聚体形式结合到ParDE的启动子上。在小鼠感染模型中,ZY05719中ParDE的缺失显著减弱了毒力。ΔparDE还表现出抗氧化应激能力降低,并且ΔparDE更容易被巨噬细胞吞噬和杀伤。此外,与ZY05719相比,ΔparDE菌株的生物膜形成能力显著增强。综上所述,这些发现表明II型TA系统ParDE在猪链球菌的致病过程中发挥着重要作用,为其致病机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/77e90d3aeae7/12917_2024_4069_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/57186792e82e/12917_2024_4069_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/02c2c59123ae/12917_2024_4069_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/77e90d3aeae7/12917_2024_4069_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/57186792e82e/12917_2024_4069_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/5b5d7b7ab750/12917_2024_4069_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/02c2c59123ae/12917_2024_4069_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/6ed8205958f7/12917_2024_4069_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0771/11744833/77e90d3aeae7/12917_2024_4069_Fig5_HTML.jpg

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本文引用的文献

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Toxin:antitoxin ratio sensing autoregulation of the module.毒素:抗毒素比值感应模块的自身调节。
Sci Adv. 2024 Jan 5;10(1):eadj2403. doi: 10.1126/sciadv.adj2403.
2
Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition.条件性重塑结核分枝杆菌 ParDE1 导致毒素释放,从而抑制拓扑异构酶。
Nucleic Acids Res. 2024 Feb 28;52(4):1909-1929. doi: 10.1093/nar/gkad1220.
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Orphan response regulator CovR plays positive regulative functions in the survivability and pathogenicity of Streptococcus suis serotype 2 isolated from a pig.
从猪体分离的 2 型猪链球菌孤儿反应调节子 CovR 对其生存力和致病性具有正调控作用。
BMC Vet Res. 2023 Nov 22;19(1):243. doi: 10.1186/s12917-023-03808-9.
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Methyl anthranilate deteriorates biofilm structure of Streptococcus suis and antagonizes the capsular polysaccharide defence effect.甲基氨基苯甲酸破坏猪链球菌生物膜结构并拮抗荚膜多糖的防御作用。
Int J Antimicrob Agents. 2023 Dec;62(6):106996. doi: 10.1016/j.ijantimicag.2023.106996. Epub 2023 Oct 1.
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Mycobacterium abscessus VapC5 toxin potentiates evasion of antibiotic killing by ribosome overproduction and activation of multiple resistance pathways.脓肿分枝杆菌 VapC5 毒素通过核糖体过度产生和激活多种耐药途径增强了逃避抗生素杀伤的能力。
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A ParDE toxin-antitoxin system is responsible for the maintenance of the virulence plasmid but not for type III secretion-associated growth inhibition.一个 ParDE 毒素-抗毒素系统负责维持毒性质粒,但与 III 型分泌系统相关的生长抑制无关。
Front Cell Infect Microbiol. 2023 May 9;13:1166077. doi: 10.3389/fcimb.2023.1166077. eCollection 2023.
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eDNA-stimulated cell dispersion from biofilms upon oxygen limitation is dependent on a toxin-antitoxin system.在氧限制条件下,eDNA 刺激生物膜中的细胞分散依赖于毒素-抗毒素系统。
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Comparative virulence and antimicrobial resistance distribution of isolates obtained from the United States.从美国获得的分离株的比较毒力和抗菌药物耐药性分布
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