Choi Won-Sik, Lee Tae Hun, Son Se Jin, Kim Tae Gyu, Kwon Byoung-Mog, Son Hyeong-U, Kim Sung Uk, Lee Sang-Han
Research Institute, JeonjinBio Co., Ltd, Daegu, Korea.
Department of Nano Science and Technology, Graduate School, Kyungpook National University, Daegu, Korea.
J Antibiot (Tokyo). 2017 Nov;70(11):1065-1069. doi: 10.1038/ja.2017.98. Epub 2017 Sep 6.
In many pathogenic Gram-negative bacteria, such as Salmonella, Escherichia coli, Yersinia and Chlamydia spp., which cause diseases in humans, the type III secretion system (TTSS) is an important virulence factor that translocates effector proteins into the cytosol of host cells. Thus, the TTSS is a good target for antibacterial agents. Here we used a hemolysis assay to search for TTSS inhibitors and found that a compound from Magnolia obovata called obovatol blocks the TTSS of Salmonella. Obovatol showed potent inhibitory activity (IC=19.8 μM) against the TTSS-related hemolysis of Salmonella, which was not due to a reduction of bacterial growth. Instead, the compound inhibited bacterial motility, TTSS-related mRNA expression and effector protein secretion. These data demonstrate the inhibitory effect of obovatol on the Salmonella TTSS and suggest that it could be useful for the prevention and supplementary treatment of bacterial infections.
在许多致病性革兰氏阴性细菌中,如沙门氏菌、大肠杆菌、耶尔森氏菌和衣原体属,这些细菌会引发人类疾病,III型分泌系统(TTSS)是一种重要的毒力因子,可将效应蛋白转运到宿主细胞的胞质溶胶中。因此,TTSS是抗菌剂的良好靶点。在这里,我们使用溶血试验来寻找TTSS抑制剂,发现来自日本厚朴的一种名为奥巴托醇的化合物可阻断沙门氏菌的TTSS。奥巴托醇对沙门氏菌与TTSS相关的溶血表现出强大的抑制活性(IC = 19.8 μM),这并非由于细菌生长减少所致。相反,该化合物抑制细菌运动、与TTSS相关的mRNA表达和效应蛋白分泌。这些数据证明了奥巴托醇对沙门氏菌TTSS的抑制作用,并表明它可能对细菌感染的预防和辅助治疗有用。