Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection

详细信息    查看全文

• 作者：Hongen Li^a ; ¹ ; Yutao Chen^b ; ¹ ; Bing Zhang^a ; ¹ ; Xiaodi Niu^a ; Meng Song^a ; Zhaoqing Luo^c ; Gejin Lu^a ; Bowen Liu^a ; Xiaoran Zhao^a ; Jianfeng Wang^a ; ^{wjf927@jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xuming Deng^a ; ^{dengxm@jlu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Listeria monocytogenes ; Sortase A ; Chalcone ; Anti-infection
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：106
• 期：Complete
• 页码：19-29
• 全文大小：3530 K

文摘

The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC₅₀ of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection.