Orientin mediates protection against MRSA-induced pneumonia by inhibiting Sortase A.
Orientin mediates protection against MRSA-induced pneumonia by inhibiting Sortase A.
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Orientin 通过抑制 Sortase A 介导针对 MRSA 诱导的肺炎的保护作用
DOI：
10.1080/21505594.2021.1962138
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Wang L;Jing S;Qu H;Wang K;Jin Y;Ding Y;Yang L;Yu H;Shi Y;Li Q;Wang D
耐药致病性金黄色葡萄球菌（S.金黄色葡萄球菌（aureus）已严重威胁人类健康，引起广泛关注。分选酶A（Sortase A，SrtA）是S.金黄色葡萄球菌，其负责将多种毒力相关蛋白共价锚定到细胞壁。SrtA一直被认为是抗沙门氏菌的理想药理学靶点。金黄色葡萄球菌感染。在本研究中，我们确定了从各种药用植物中分离的天然化合物Orientin可以有效地抑制SrtA的活性，IC 50为50.44 ± 0.51 µM。我们进一步证明了Orientin抑制S.金黄色葡萄球菌的纤维蛋白原和减少生物膜的形成和附着的葡萄球菌蛋白A（SpA）的细胞壁在体外。使用荧光猝灭法，我们证明了Orientin和SrtA之间的直接相互作用。进一步的机制研究表明，Glu-105、Thr-93和Cys-184是SrtA与Orientin结合的关键位点。重要的是，我们证明了用Orientin治疗可以减弱S。金黄色葡萄球菌的体内毒力和保护小鼠免受S.金黄色葡萄球菌引起的致命性肺炎这些结果表明，Orientin是一种潜在的抗S。金黄色葡萄球菌感染和限制耐药性的发展。
Drug-resistant pathogenic Staphylococcus aureus (S. aureus) has severely threatened human health and arouses widespread concern. Sortase A (SrtA) is an essential virulence factor of S. aureus, which is responsible for the covalent anchoring of a variety of virulence-related proteins to the cell wall. SrtA has always been regarded as an ideal pharmacological target against S. aureus infections. In this research, we have determined that orientin, a natural compound isolated from various medicinal plants, can effectively inhibit the activity of SrtA with an IC50 of 50.44 ± 0.51 µM. We further demonstrated that orientin inhibited the binding of S. aureus to fibrinogen and diminished biofilm formation and the attaching of Staphylococcal protein A (SpA) to the cell wall in vitro. Using the fluorescence quenching assay, we demonstrated a direct interaction between orientin and SrtA. Further mechanistic studies revealed that the residues Glu-105, Thr-93, and Cys-184 were the key sites for the binding of SrtA to orientin. Importantly, we demonstrated that treatment with orientin attenuated S. aureus virulence of in vivo and protected mice against S. aureus-induced lethal pneumonia. These findings indicate that orientin is a potential drug to counter S. aureus infections and limit the development of drug resistance.
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影响因子：
1.6
作者：
Kim, SH;Shin, DS;Oh, KB
通讯作者：
Oh, KB
影响因子：
2
作者：
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作者：
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