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Bilobetin attenuates Staphylococcus aureus virulence by targeting Von Willebrand factor-binding protein and staphylocoagulase

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Abstract

Staphylococcus aureus (S. aureus) induces a variety of infectious diseases in humans and animals and is responsible for hospital- and community-acquired infections. The aim of this study was to investigate how bilobetin, a natural compound, attenuates S. aureus virulence by inhibiting two key virulence factors, von Willebrand factor-binding protein (vWbp) and staphylocoagulase (Coa). The results showed that bilobetin inhibited Coa- or vWbp-induced coagulation without affecting S. aureus proliferation. The Western blotting and fluorescence quenching assays indicated that bilobetin did not affect the expression of vWbp and Coa but directly bound to the proteins with KA values of 1.66 × 104 L/mol and 1.04 × 104 L/mol, respectively. To gain further insight into the mechanism of interaction of bilobetin with these virulence factors, we performed molecular docking and point mutation assays, which indicated that the TYR-6 and TYR-18 residues on vWbp and the ALA-190 and ASP-189 residues on Coa were essential for the binding of bilobetin. In addition, the in vivo studies showed that bilobetin ameliorated lung tissue damage and inflammation caused by S. aureus, thereby improving the survival of mice. Furthermore, the use of bilobetin as an adjuvant in combination with vancomycin was more effective in the treatment of a mouse model of pneumonia. Taken together, bilobetin had a dual inhibitory effect on vWbp and Coa by reducing the virulence of S. aureus, suggesting that it is a viable lead compound against S. aureus infections.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was partly supported by the National Natural Science Foundation of China (Grant No. 81860567), Science and Technology Development Plan Project of Jilin Province Science and Technology Department (Grant No.20200404085YY), “Xinglin Scholar Project” of Changchun University of Chinese Medicine (QNKXJ2-2021ZR05) and Technology Project of Education Department of Jilin Province (No. JJKH20230985KJ).

Funding

Science and Technology Development Plan Project of Jilin Province Science and Technology Department, Grant/Award Number: No.20200404085YY, “Xinglin Scholar Project” of Changchun University of Chinese Medicine/Award Number: QNKXJ2-2021ZR05, Technology Project of Education Department of Jilin Province/Award Number: No. JJKH20230985KJ.

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Author notes

  1. Chongling Zhang and Wenyuan Zhang contributed equally.

Authors and Affiliations

  1. Changchun University of Chinese Medicine, Changchun, China

    Chongling Zhang, Wenyuan Zhang, Shuyue Zhu, Sihua Che, Meiling Wang, Mengli Jin, Nan Bian, Wu Song, Shuang Jiang, Yijing Jiang, Juan Hou, Chang Liu, Haofang Zhou, Lin Wei, Guijun Shi & Yong Tang

  2. Proctology Department, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China

    Chunjie Hu

  3. Changchun Hospital of Traditional Chinese Medicine, Changchun, China

    Guijun Shi

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  1. Chongling Zhang
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  2. Wenyuan Zhang
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Contributions

W.S., Y.T., G.J.S. and L.W.: conceived and designed research. C.L.Z., W.Y.Z., S.Y.Z., C.J.H. and S.C.: experimentalize. M.L.W., Y.J.J., M.L.J., B.N. and C.L.: analyzed data. S.J., J.H., and H.F.Z.: writing the manuscript. All authors commented on previous versions of the manuscript and approved the final version.

Corresponding authors

Correspondence to Lin Wei, Guijun Shi or Yong Tang.

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Ethics statement

Animal experiments were conducted in strict compliance with the ARRIVE guidelines and the guidelines of the Animal Ethics Committee of Changchun University of Chinese Medicine.

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Zhang, C., Zhang, W., Zhu, S. et al. Bilobetin attenuates Staphylococcus aureus virulence by targeting Von Willebrand factor-binding protein and staphylocoagulase. World J Microbiol Biotechnol 39, 358 (2023). https://doi.org/10.1007/s11274-023-03812-z

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