Institute of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou 121001, P.R. China.
Department of Pharmacy, Tianjin Baodi Hospital, Baodi Clinical College, Tianjin Medical University, Tianjin 301800, P.R. China.
J Microbiol Biotechnol. 2022 Oct 28;32(10):1284-1291. doi: 10.4014/jmb.2206.06007. Epub 2022 Oct 7.
The rise of methicillin-resistant (MRSA) has resulted in significant morbidity and mortality, and clinical treatment of MRSA infections has become extremely difficult. Sortase A (SrtA), a virulence determinant that anchors numerous virulence-related proteins to the cell wall, is a prime druggable target against infection due to its crucial role in the pathogenicity of . Here, we demonstrate that isovitexin, an active ingredient derived from a variety of traditional Chinese medicines, can reversibly inhibit SrtA activity in vitro with a low dose (IC=24.72 μg/ml). Fluorescence quenching and molecular simulations proved the interaction between isovitexin and SrtA. Subsequent point mutation experiments further confirmed that the critical amino acid positions for SrtA binding to isovitexin were Ala-92, Ile-182, and Trp-197. In addition, isovitexin treatment dramatically reduced invasion of A549 cells. This study shows that treatment with isovitexin could alleviate pathological injury and prolong the life span of mice in an pneumonia model. According to our research, isovitexin represents a promising lead molecule for the creation of anti- medicines or adjuncts.
耐甲氧西林金黄色葡萄球菌（MRSA）的出现导致了发病率和死亡率的显著增加，而对 MRSA 感染的临床治疗已变得极其困难。天冬酰胺酰内肽酶 A（SrtA）是一种毒力决定因素，可将许多与毒力相关的蛋白质锚定到细胞壁上，由于其在感染中的关键作用，是针对感染的一个主要可成药靶标。在这里，我们证明了异牡荆黄素，一种源自多种中药的活性成分，可在低剂量（IC=24.72μg/ml）下体外可逆抑制 SrtA 活性。荧光猝灭和分子模拟证明了异牡荆黄素与 SrtA 之间的相互作用。随后的点突变实验进一步证实了 SrtA 与异牡荆黄素结合的关键氨基酸位置为 Ala-92、Ile-182 和 Trp-197。此外，异牡荆黄素处理可显著降低 A549 细胞的侵袭。这项研究表明，异牡荆黄素治疗可减轻肺炎模型中小鼠的病理损伤并延长其寿命。根据我们的研究，异牡荆黄素代表了一种有前途的先导分子，可用于开发抗药或辅助药物。
