Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Virulence. 2021 Dec;12(1):2659-2669. doi: 10.1080/21505594.2021.1981000.
Enterotoxigenic (ETEC) is a leading cause of diarrheal disease in developing nations where it accounts for a significant disease burden in children between the ages of 0 to 59 months. It is also the number one bacterial causative agent of traveler's diarrhea. ETEC infects hosts through the fecal-oral route and utilizes colonization factors (CF) to adhere within the small intestine. Over 25 CFs have been identified; 7 are considered major CFs and a vaccine targeting these is predicted to provide protection against up to 66% of ETEC associated disease. Coli Surface Antigen 6 (CS6) is a major CF and is associated with disease-causing ETEC isolates. Analysis of the CS6 operon sequence led to the identification of two regions of variability among clinical isolates which we predicted exert effects on CS6 transcript and protein expression. A total of 7 recombinant strains were engineered to encode the CS6 operon in wild-type, hybrid, and mutant configurations. Western blot analysis and RT-qPCR provided evidence to support the importance of an intergenic hairpin structure on CS6 expression. Our results reveal the significance of CS6 sequence selection regarding ETEC vaccine development and present novel information regarding CS6 sequence variation in WT ETEC strains.
肠产毒性大肠杆菌（ETEC）是发展中国家腹泻病的主要病因，在 0 至 59 月龄儿童中造成了巨大的疾病负担。它也是旅行者腹泻的头号细菌性病原体。ETEC 通过粪-口途径感染宿主，并利用定植因子（CF）在小肠内附着。已经确定了超过 25 种 CF，其中 7 种被认为是主要 CF，针对这些 CF 的疫苗预计将提供高达 66%的 ETEC 相关疾病的保护。大肠杆菌表面抗原 6（CS6）是一种主要的 CF，与引起疾病的 ETEC 分离株有关。对 CS6 操纵子序列的分析导致在临床分离株中鉴定出两个变异区，我们预测这些变异区会对 CS6 转录物和蛋白质表达产生影响。总共设计了 7 种重组菌株，以野生型、杂交型和突变型配置来编码 CS6 操纵子。Western blot 分析和 RT-qPCR 提供了证据，支持 CS6 表达中基因间发夹结构的重要性。我们的结果揭示了 CS6 序列选择对 ETEC 疫苗开发的重要性，并提供了关于 WT ETEC 菌株中 CS6 序列变异的新信息。
