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Biochemical Pharmacology-13 May 2020 黃芩素

時(shí)間：2020-09-03 瀏覽次數(shù)：分享到：

Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp

期刊名：Biochemical Pharmacology
文獻(xiàn)編號(hào)：DOI 10.1016/j.bcp.2020.114024
文獻(xiàn)地址：https://www.sciencedirect.com/science/article/abs/pii/S0006295220302513?via%3Dihub
發(fā)表日期：13 May 2020

Abstract
The emergence and spread of multidrug-resistant Staphylococcus aureus (S. aureus) necessitate the research on therapeutic tactics which are different from classical antibiotics in overcoming resistance and treating infections. In S. aureus, von Willebrand factor-binding protein (vWbp) is one of the key virulence determinants because it mediates not only the activation of thrombin to convert fibrinogen to fibrin, thereby enabling S. aureus to escape from the host immune clearance, but also the adhesion of S. aureus to host cells. Thus, vWbp is regarded as a promising druggable target to treat S. aureus-associated infections. Here we identify that baicalein, a natural compound isolated from the Chinese herb Scutellaria baicalensis, can effectively block the coagulase activity of vWbp without inhibiting the growth of the bacteria. Through thermal shift and fluorescence quenching assays, we demonstrated that baicalein directly binds to vWbp. Molecular dynamics simulations and mutagenesis assays revealed that the Asp-75 and Lys-80 residues are necessary for baicalein binding to vWbp. Importantly, we demonstrated that baicalein treatment attenuates the virulence of S. aureus and protects mice from S. aureus-induced lethal pneumonia. In addition, baicalein can improve the therapeutic effect of penicillin G by 75% in vivo. These findings indicate that baicalein might be developed as a promising therapeutic agent against drug-resistant S. aureus infections.

Baicalein was purchased from Chengdu Desite Biological Technology Co. Ltd (Wenjiang District, Chengdu, China)

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