<i>Abiotrophia defectiva</i> DnaK Promotes Fibronectin-Mediated Adherence to HUVECs and Induces a Proinflammatory Response

• Main Authors: Minoru Sasaki, Yu Shimoyama, Yoshitoyo Kodama, Taichi Ishikawa
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Abiotrophia defectiva</i>; DnaK; fibronectin-binding protein; HUVECs; proinflammatory response
• Online Access: https://www.mdpi.com/1422-0067/22/16/8528

<i>Abiotrophia defectiva</i> is a nutritionally variant streptococci that is found in the oral cavity, and it is an etiologic agent of infective endocarditis. We have previously reported the binding activity of <i>A. defectiva</i> to fibronectin and to human umbilical vein endothelial cells (HUVECs). However, the contribution of some adhesion factors on the binding properties has not been well delineated. In this study, we identified DnaK, a chaperon protein, as being one of the binding molecules of <i>A. defectiva</i> to fibronectin. Recombinant DnaK (rDnaK) bound immobilized fibronectin in a concentration-dependent manner, and anti-DnaK antiserum reduced the binding activity of <i>A. defectiva</i> with both fibronectin and HUVECs. Furthermore, DnaK were observed on the cell surfaces via immune-electroscopic analysis with anti-DnaK antiserum. Expression of IL-8, CCL2, ICAM-1, and VCAM-1 was upregulated with the <i>A. defectiva</i> rDnaK treatment in HUVECs. Furthermore, TNF-α secretion of THP-1 macrophages was also upregulated with the rDnaK. We observed these upregulations in rDnaK treated with polymyxin B, but not in the heat-treated rDnaK. The findings show that <i>A. defectiva</i> DnaK functions not only as an adhesin to HUVECs via the binding to fibronectin but also as a proinflammatory agent in the pathogenicity to cause infective endocarditis.