Galangin as a direct inhibitor of vWbp protects mice from Staphylococcus aureus‐induced pneumonia

• Published in: Journal of cellular and molecular medicine Vol. 26; no. 3; pp. 828 - 839
• Main Authors: Jin, Yingli, Yang, Panpan, Wang, Li, Gao, Zeyuan, Lv, Jia, Cui, Zheyu, Wang, Tiedong, Wang, Dacheng, Wang, Lin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2022; John Wiley and Sons Inc
• Subjects: Adjuvants; Animals; Antibiotics; Bacterial infections; Bioactive compounds; Biotechnology industry; Carrier Proteins - metabolism; Cell walls; Coagulase; Drug development; E coli; Endocarditis; Endothelial cells; Endothelial Cells - metabolism; Fibrin; Flavonoids - therapeutic use; galangin; Laboratories; Mice; Multidrug resistance; Mutagenesis; Original; Pneumonia; Proteins; Prothrombin; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus infections; Virulence; Von Willebrand factor; von Willebrand Factor - antagonists & inhibitors; von Willebrand Factor - metabolism; von Willebrand factor‐binding protein; pneumonia; galangin; Staphylococcus aureus; von Willebrand factor-binding protein
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17129

The surge in multidrug resistance in Staphylococcus aureus (S. aureus) and the lag in antibiotic discovery necessitate the development of new anti‐infective strategies to reduce S. aureus infections. In S. aureus, von Willebrand factor‐binding protein (vWbp) is not only the main coagulase that triggers host prothrombin activation and formation of fibrin cables but also bridges the bacterial cell wall and von Willebrand factor, thereby allowing S. aureus to bind to platelets and endothelial cells, playing a vital role in pathogenesis of S. aureus infections. Here, we have identified that galangin, a bioactive compound found in honey and Alpinia officinarum Hance, is a potent and direct inhibitor of vWbp by coagulation activity inhibition assay, thermal shift assay and biolayer interferometry assay. Molecular dynamic simulations and verification experiments revealed that the Trp‐64 and Leu‐69 residues are necessary for the binding of galangin to vWbp. Significantly, galangin attenuated S. aureus virulence in a mouse S. aureus‐induced pneumonia model. In addition, we also identified that galangin can enhance the therapeutic effect of latamoxef on S. aureus‐induced pneumonia. Taken together, the results suggest that galangin may be used for the development of therapeutic drugs or utilized as adjuvants to combine with antibiotics to combat S. aureus‐related infections.