2. Academic Validation
  3. An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia

An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia

  • Front Microbiol. 2019 Jan 23;10:7. doi: 10.3389/fmicb.2019.00007.
Bangbang Li 1,  Yingli Jin 1,  Hua Xiang 2 3,  Dan Mu 4,  Panpan Yang 1,  Xianmei Li 4,  Ling Zhong 4,  Junjie Cao 4,  Dan Xu 5,  Qian Gong 6,  Tiedong Wang 4,  Lin Wang 7,  Dacheng Wang 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China.
  • 2 College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
  • 3 Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China.
  • 4 College of Animal Sciences, Jilin University, Changchun, China.
  • 5 Shen Yang Weijia Animal Husbandry Company Limited, Shenyang, China.
  • 6 College of Humanities & Sciences of Northeast Normal University, Changchun, China.
  • 7 Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
PMID: 30728809 DOI: 10.3389/fmicb.2019.00007
Abstract

Von Willebrand factor-binding protein (vWbp), secreted by Staphylococcus aureus (S. aureus), can activate host prothrombin, convert fibrinogen to fibrin clots, induce blood clotting, and contribute to pathophysiology of S. aureus-related diseases, including infective endocarditis, staphylococcal sepsis and pneumonia. Therefore, vWbp is an promising drug target in the treatment of S. aureus-related infections. Here, we report that dryocrassin ABBA (ABBA), a natural compound derived from Dryopteris crassirhizoma, can significantly inhibit the coagulase activity of vWbp in vitro by directly interacting with vWbp without killing the bacteria or inhibiting the expression of the vWbp. Using molecular dynamics simulations, we demonstrate that ABBA binds to the "central cavity" in the elbow of vWbp by interacting with Arg-70, His-71, Ala-72, Gly-73, Tyr-74, Glu-75, Tyr-83, and Gln-87 in vWbp, thus interfering with the binding of vWbp to prothrombin. Furthermore, in vivo studies demonstrated that ABBA can attenuate injury and inflammation of mouse lung tissues caused by S. aureus and increase survival of mice. Together these findings indicate that ABBA is a promising lead drug for the treatment of S. aureus-related infections. This is the first report of potential inhibitor which inhibit the coagulase activity of vWbp by directly interacting with vWbp.

Keywords

Staphylococcus aureus; direct inhibitor; dryocrassin ABBA; pneumonia; von Willebrand factor-binding protein.

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