Glaesserella parasuis serotype 4 exploits fibronectin via RlpA for tracheal colonization following porcine circovirus type 2 infection

IF 6.7 1区 医学 Q1 Immunology and Microbiology PLoS Pathogens Pub Date : 2024-09-12 DOI:10.1371/journal.ppat.1012513
Mengru Guo, Yuhui Li, Jinsheng Tang, Qing Wang, Qiancheng Wang, Hong Zhou, Huixing Lin, Zhe Ma, Hongjie Fan
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Abstract

Porcine circovirus type 2 (PCV2) often causes disease through coinfection with other bacterial pathogens, including Glaesserella parasuis (G. parasuis), which causes high morbidity and mortality, but the role played by PCV2 and bacterial and host factors contributing to this process have not been defined. Bacterial attachment is assumed to occur via specific receptor-ligand interactions between adhesins on the bacterial cell and host proteins adsorbed to the implant surface. Mass spectrometry (MS) analysis of PCV2-infected swine tracheal epithelial cells (STEC) revealed that the expression of Extracellular matrix protein (ECM) Fibronectin (Fn) increased significantly on the infected cells surface. Importantly, efficient G. parasuis serotype 4 (GPS4) adherence to STECs was imparted by interactions with Fn. Furthermore, abrogation of adherence was gained by genetic knockout of Fn, Fn and Integrin β1 antibody blocking. Fn is frequently exploited as a receptor for bacterial pathogens. To explore the GPS4 adhesin that interacts with Fn, recombinant Fn N-terminal type I and type II domains were incubated with GPS4, and the interacting proteins were pulled down for MS analysis. Here, we show that rare lipoprotein A (RlpA) directly interacts with host Fibronectin mediating GPS4 adhesion. Finally, we found that PCV2-induced Fibronectin expression and adherence of GPS4 were prevented significantly by TGF-β signaling pathway inhibitor SB431542. Our data suggest the RlpA-Fn interaction to be a potentially promising novel therapeutic target to combat PCV2 and GPS4 coinfection.
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猪 2 型圆环病毒感染后,寄生虫 4 号血清型通过 RlpA 利用纤维粘连蛋白进行气管定植
猪圆环病毒 2 型(PCV2)经常通过与其他细菌病原体(包括寄生璃泽氏菌(G. parasuis))合并感染而致病,造成很高的发病率和死亡率,但 PCV2 在这一过程中所起的作用以及导致这一过程的细菌和宿主因素尚未明确。据推测,细菌的附着是通过细菌细胞上的粘附素与吸附在种植体表面的宿主蛋白质之间的特异性受体-配体相互作用而发生的。对感染 PCV2 的猪气管上皮细胞(STEC)进行的质谱分析表明,受感染细胞表面细胞外基质蛋白(ECM)纤连蛋白(Fn)的表达量显著增加。重要的是,寄生虫血清型 4(GPS4)通过与 Fn 相互作用而有效地粘附在 STEC 上。此外,通过基因敲除 Fn、Fn 和 Integrin β1 抗体阻断,也能减弱粘附性。Fn 经常被用作细菌病原体的受体。为了探索与Fn相互作用的GPS4粘附蛋白,将重组的Fn N端I型和II型结构域与GPS4孵育,并将相互作用的蛋白拉下来进行质谱分析。在这里,我们发现稀有脂蛋白 A(RlpA)直接与宿主纤连蛋白相互作用,介导 GPS4 的粘附。最后,我们发现 TGF-β 信号通路抑制剂 SB431542 能显著阻止 PCV2 诱导的纤连蛋白表达和 GPS4 的粘附。我们的数据表明,RlpA-Fn 相互作用可能是对抗 PCV2 和 GPS4 协同感染的一个很有前景的新治疗靶点。
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来源期刊
PLoS Pathogens
PLoS Pathogens 生物-病毒学
CiteScore
11.40
自引率
3.00%
发文量
598
审稿时长
2 months
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
期刊最新文献
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