Kauppi Anna M, Nordfelth Roland, Uvell Hanna, Wolf-Watz Hans, Elofsson Mikael
Organic Chemistry, Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
Chem Biol. 2003 Mar;10(3):241-9. doi: 10.1016/s1074-5521(03)00046-2.
Agents that target bacterial virulence without detrimental effect on bacterial growth are useful chemical probes for studies of virulence and potential candidates for drug development. Several gram-negative pathogens employ type III secretion to evade the innate immune response of the host. Screening of a chemical library with a luciferase reporter gene assay in viable Yersinia pseudotuberculosis furnished several compounds that inhibit the reporter gene signal expressed from the yopE promoter and effector protein secretion at concentrations with no or modest effect on bacterial growth. The selectivity patterns observed for inhibition of various reporter gene strains indicate that the compounds target the type III secretion machinery at different levels. Identification of this set of inhibitors illustrates the approach of utilizing cell-based assays to identify compounds that affect complex bacterial virulence systems.
靶向细菌毒力而对细菌生长无有害影响的试剂，是用于毒力研究的有用化学探针以及药物开发的潜在候选物。几种革兰氏阴性病原体利用III型分泌来逃避宿主的先天免疫反应。用荧光素酶报告基因检测法对活的假结核耶尔森氏菌中的化学文库进行筛选，得到了几种化合物，这些化合物在对细菌生长无影响或影响不大的浓度下，抑制从yopE启动子表达的报告基因信号以及效应蛋白分泌。对各种报告基因菌株抑制作用观察到的选择性模式表明，这些化合物在不同水平上靶向III型分泌机制。这组抑制剂的鉴定说明了利用基于细胞的检测方法来鉴定影响复杂细菌毒力系统的化合物的方法。
