1. Glaesserella parasuis serotype 4 exploits fibronectin via RlpA for tracheal colonization following porcine circovirus type 2 infection.
- Author
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Guo, Mengru, Li, Yuhui, Tang, Jinsheng, Wang, Qing, Wang, Qiancheng, Zhou, Hong, Lin, Huixing, Ma, Zhe, and Fan, Hongjie
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EXTRACELLULAR matrix proteins ,BACTERIAL adhesion ,BACTERIAL adhesins ,BACTERIAL cells ,EPITHELIAL cells ,PORCINE reproductive & respiratory syndrome - 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. Author summary: Porcine circovirus type 2 and Glaesserella parasuis (G. parasuis) are common upper respiratory tract pathogens in pigs, which co-infection causes high morbidity and mortality. However, the underlying mechanisms of host-pathogen interactions during PCV2 and GPS4 co-infection remain unclear. Here, we focused on the interaction of PCV2-infected cells and GPS4, which revealed that swine tracheal epithelial cells (STEC) infected with PCV2 exhibit the increased expression of Fn. Notably, PCV2 infection-induced Fn interacting with RlpA was shown to impart efficient adherence to GPS4. Fn and Integrin β1 antibody blocking and SB431542 counteracted PCV2 infection-induced GPS4 colonization. These studies reveal a novel receptor-ligand interaction that enhances colonization of the tracheal by GPS4 following PCV2 infection and highlights the importance of Fn-RlpA in host-pathogen interactions. In addition, RlpA was discovered for the first time as an adhesin of GPS4, which provided a new idea for the development of G. parasuis vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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