Department of Microbiology and Immunology, University of Miami Miller School of Medicine, P.O. Box 016960 (R-138), Miami, FL, 33101, USA,
Immunol Res. 2013 Dec;57(1-3):229-36. doi: 10.1007/s12026-013-8453-4.
Enterotoxigenic Escherichia coli is frequently associated with travelers' diarrhea and is a leading cause of infant and childhood mortality in developing countries. Disease is dependent upon the orchestrated expression of enterotoxins, flexible adhesive pili, and other virulence factors. Both the heat-labile (LT) and heat-stable (ST-H) enterotoxins are regulated at the level of transcription by cAMP-receptor protein which represses the expression of LT while activating expression of ST-H. The expression of many different serotypes of adhesive pili is regulated by Rns, a member of the AraC family that represents a subgroup of conserved virulence regulators from several enteric pathogens. These Rns-like regulators recognize similar DNA binding sites, and a compiled sequence logo suggests they may bind DNA through both major and minor groove interactions. These regulators are also tempting targets for novel therapeutics because they play pivotal roles during infection. To that end, high-throughput screens have begun to identify compounds that inhibit the activity of these regulators, predominately by interfering with DNA binding.
产肠毒素性大肠杆菌常与旅行者腹泻有关，也是发展中国家婴儿和儿童死亡的主要原因。疾病的发生依赖于肠毒素、灵活的粘附性菌毛和其他毒力因子的协调表达。热不稳定 (LT) 和热稳定 (ST-H) 肠毒素都是通过 cAMP 受体蛋白在转录水平上调节的，该蛋白抑制 LT 的表达，同时激活 ST-H 的表达。许多不同血清型粘附菌毛的表达受 Rns 调节，Rns 是 AraC 家族的成员，代表了几种肠病原体中保守毒力调节剂的一个亚群。这些 Rns 样调节剂识别相似的 DNA 结合位点，并且编译的序列标志表明它们可能通过主沟和小沟相互作用结合 DNA。这些调节剂也是新型治疗药物的诱人目标，因为它们在感染过程中起着关键作用。为此，高通量筛选已开始识别抑制这些调节剂活性的化合物，主要通过干扰 DNA 结合。
