Institute of Biomedicine for Brazilian Semiarid, Federal University of Ceará, 1315 Coronel Nunes de Melo, 60430-270, Fortaleza, Brazil.
Institute of Biomedicine for Brazilian Semiarid, Federal University of Ceará, 1315 Coronel Nunes de Melo, 60430-270, Fortaleza, Brazil.
Int J Med Microbiol. 2019 Mar;309(2):151-158. doi: 10.1016/j.ijmm.2019.01.003. Epub 2019 Jan 31.
Shigella/Enteroinvasive Escherichia coli (EIEC) pathotype is a major enteropathogen associated with diarrhea and malnutrition in children from developing countries. This study aimed to correlate Shigella/EIEC virulence-related genes (VRGs) with clinical symptoms, nutritional status and coenteropathogens in children from the Brazilian semiarid region. We designed a case-control study of community diarrhea in six cities of the Brazil semiarid region with 1200 children aging 2-36 months. Standardized questionnaire was applied for collecting sociodemographic, nutritional status and clinical information of the children. DNA samples were extracted from stools and diagnosed for Shigella/EIEC using PCR-based approaches. Positive samples were tested for 28 VRGs using four multiplex PCRs. Intestinal inflammation was determined by measuring fecal myeloperoxidase (MPO). Shigella/EIEC pathotype was detected in 5% of the children and was significantly associated with diarrhea. The genes sen (encoding Shigella enterotoxin 2), ipgB2, ipgB1 (both encoding type 3 secretion system-T3SS effectors that modulate actin filament), and ospF (encoding a T3SS effector involved in suppression of host responses) were further associated with diarrhea in Shigella/EIEC positive children. Among children presenting diarrhea, virA gene (encoding a T3SS effector that promotes microtubule destabilization) was associated with fever, while virB (encoding a major transcriptional activator) was associated with low height-for-age z-score. In addition, these VRGs were associated with increased fecal MPO, and coinfection with Salmonella spp. was associated with increased abdominal pain. These data reinforce the impact of Shigella/EIEC on diarrhea in children from Brazilian semiarid region and highlighted the contributions of specific virulence genes for its pathobiology.
志贺氏/侵袭性大肠杆菌（EIEC）血清型是与发展中国家儿童腹泻和营养不良相关的主要肠道病原体。本研究旨在探讨巴西半干旱地区儿童中志贺氏/侵袭性大肠杆菌毒力相关基因（VRGs）与临床症状、营养状况和共同肠道病原体的相关性。我们设计了一项巴西半干旱地区 6 个城市社区腹泻的病例对照研究，共纳入 1200 名 2-36 月龄儿童。采用标准化问卷收集儿童的社会人口统计学、营养状况和临床信息。从粪便中提取 DNA 样本，采用基于 PCR 的方法诊断志贺氏/侵袭性大肠杆菌。对阳性样本进行 28 个 VRGs 的检测，采用 4 重多重 PCR 法。通过测量粪便髓过氧化物酶（MPO）来确定肠道炎症。在 5%的儿童中检测到志贺氏/侵袭性大肠杆菌血清型，且与腹泻显著相关。sen（编码志贺氏肠毒素 2）、ipgB2、ipgB1（均编码 3 型分泌系统-T3SS 效应子，调节肌动蛋白丝）和 ospF（编码一种参与抑制宿主反应的 T3SS 效应子）基因与志贺氏/侵袭性大肠杆菌阳性儿童的腹泻进一步相关。在出现腹泻的儿童中，virA 基因（编码一种促进微管不稳定的 T3SS 效应子）与发热相关，而 virB 基因（编码主要转录激活因子）与身高年龄 Z 评分低相关。此外，这些 VRGs 与粪便 MPO 增加有关，与沙门氏菌属的合并感染与腹痛增加有关。这些数据强调了志贺氏/侵袭性大肠杆菌对巴西半干旱地区儿童腹泻的影响，并突出了特定毒力基因在其发病机制中的作用。
