College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, China.
School of Basic Medical Sciences, Beihua University, Jilin, China.
J Appl Microbiol. 2023 Sep 5;134(9). doi: 10.1093/jambio/lxad191.
Streptococcus suis seriously harms people and animals, and importantly, causes great economic losses in the pig industry. Similar to most Gram-positive pathogenic bacteria, sortase A (SrtA) of S. suis can mediate the anchoring of a variety of virulence factors that contain specific sorting sequences to the surface of the bacterial cell wall envelope and participate in pathogenicity. The purpose of this study is to clarify the molecular mechanism of epigallocatechin-3-gallate (EGCG) inhibiting S. suis SrtA and provide more evidence for the development of novel anti-S. suis infections drugs.
Through the SrtA substrate cleavage experiment, we found that the main component of green tea, EGCG, can effectively inhibit the enzyme activity of S. suis SrtA. Further, molecular docking and molecular dynamics simulation were used to clarify the molecular mechanism of its inhibitory effect, demonstrating that EGCG mainly interacts with amino acids at 113 and 115 to exert its inhibitory function. It was previously found that EGCG can inhibit the growth of S. suis and reduce the activity of suilysin and inhibit its expression. Our research reveals a new function of EGCG in S. suis infection.
Our research proves that EGCG can effectively inhibit the transpeptidase activity of SrtA. We also clarify the accompanying molecular mechanism, providing more sufficient evidence for the use of EGCG as a potential lead compound against S. suis infection.
猪链球菌严重危害人和动物健康,尤其会给养猪业造成巨大的经济损失。与大多数革兰氏阳性致病细菌类似,猪链球菌 SrtA 可介导多种包含特定分拣序列的毒力因子锚定到细菌细胞壁包膜表面,并参与致病性。本研究旨在阐明表没食子儿茶素没食子酸酯(EGCG)抑制猪链球菌 SrtA 的分子机制,为开发新型抗猪链球菌感染药物提供更多依据。
通过 SrtA 底物切割实验,我们发现绿茶的主要成分 EGCG 可有效抑制猪链球菌 SrtA 的酶活性。进一步通过分子对接和分子动力学模拟阐明其抑制作用的分子机制,表明 EGCG 主要与 113 和 115 位氨基酸相互作用发挥抑制功能。先前研究发现 EGCG 可抑制猪链球菌的生长,降低溶血素 suilysin 的活性并抑制其表达。本研究揭示了 EGCG 在猪链球菌感染中的新功能。
本研究证明 EGCG 可有效抑制 SrtA 的转肽酶活性,同时阐明伴随的分子机制,为将 EGCG 用作抗猪链球菌感染的潜在先导化合物提供了更充分的依据。