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Isovitexin Is a Direct Inhibitor of Staphylococcus aureus Coagulase

  • Xiang, Hua (College of Animal Medicine, Jilin Agricultural University) ;
  • Yang, Panpan (College of Basic Medical Science, Jilin University) ;
  • Wang, Li (College of Animal Science, Jilin University) ;
  • Li, Jiaxin (College of Animal Science, Jilin University) ;
  • Wang, Tiedong (College of Animal Science, Jilin University) ;
  • Xue, Junze (College of Animal Medicine, Jilin Agricultural University) ;
  • Wang, Dacheng (College of Animal Science, Jilin University) ;
  • Ma, Hongxia (College of Animal Medicine, Jilin Agricultural University)
  • Received : 2021.05.11
  • Accepted : 2021.08.17
  • Published : 2021.10.28

Abstract

Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.

Keywords

Acknowledgement

This work was supported by the National Key Research and Development Program of China (2018YFD0500300) and the Science Foundation of Jilin Province, China (No. 20180101276JC).

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