Regulation of EHEC virulence genes by QseA and small RNA molecules

QseA 和小 RNA 分子对 EHEC 毒力基因的调控

• 批准号: 7807910
• 负责人: Melissa Kendall
• 金额: $ 5.17万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-04 至 2010-06-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807910
• 关键词: Bacteria; Cessation of life; Colon; Complex; Cytoskeleton; DNA Sequence Rearrangement; Data; Development; Diarrhea; Disease Outbreaks; Dose; Enterocytes; Epinephrine; Escherichia; Escherichia coli EHEC; Escherichia coli Infections; Escherichia coli O157; Gene Expression Regulation; Gene Targeting; Genes; Hemolytic-Uremic Syndrome; Hormones; Hospitalization; Human; Large Intestine; Lead; Lesion; Norepinephrine; Operon; Pathogenesis; Pathogenicity Island; Production; Proteins; Regulation; Repression; Role; Shiga Toxin; Signal Transduction; Small RNA; Structure; Symptoms; System; Type III Secretion System Pathway; United States; Virulence; cellular microvillus; gastrointestinal; mortality; novel; pathogen; quorum sensing; stem; transcription factor; treatment strategy

DESCRIPTION (provided by applicant): Enterohemorrhagic E. coli (EHEC) O157:H7 causes bloody diarrhea and hemolytic uremic system (HUS) throughout the world. EHEC has a very low infectious dose, making it difficult to control epidemiologically. EHEC colonizes the large intestine where it causes attaching and effacing (AE) lesions and also produces Shiga toxins that are responsible for the major symptoms of HUS. Each year, EHEC causes more than 70,000 illnesses, 2000 hospitalizations, and 70,000 deaths in the United States alone. EHEC senses a bacterial autoinducer (AI-3) produced by the normal gastrointestinal flora, as well as the hormones epinephrine and norepinephrine produced by the host to activate expression of its virulence genes. Additional regulation of virulence genes occurs through the transcription factor QseA and small RNA molecules (sRNAs). However, many aspects concerning QseA and sRNA gene regulation, which are critical for virulence, remain poorly understood. This application represents a comprehensive effort to explore the functions of QseA and of sRNAs responsible for virulence gene regulation in EHEC. The Specific Aims are (1) To determine the mechanism of QseA activation and repression of target genes, (2) To characterize the role of QseA in EHEC virulence gene regulation, and (3) To elucidate the roles of small RNA (sRNA) molecules in post-transcriptional gene regulation in EHEC. The proposed experimental approaches will achieve a better understanding of the mechanisms employed by EHEC to activate its virulence genes and may reveal potentially novel aspects of EHEC pathogenesis. These data may ultimately lead to the development of unique treatment strategies for EHEC infection.

描述（由申请人提供）：肠出血性大肠杆菌 (EHEC) O157:H7 在全世界引起血性腹泻和溶血性尿毒症系统 (HUS)。肠出血性大肠杆菌的感染剂量非常低，因此很难从流行病学角度进行控制。 EHEC 定植于大肠，引起附着和消失 (AE) 病变，并产生导致 HUS 主要症状的志贺毒素。仅在美国，肠出血性大肠杆菌每年就会导致 70,000 多人患病、2000 人住院治疗以及 70,000 人死亡。 EHEC 感知正常胃肠道菌群产生的细菌自诱导剂 (AI-3)，以及宿主产生的肾上腺素和去甲肾上腺素激素，以激活其毒力基因的表达。毒力基因的额外调节通过转录因子 QseA 和小 RNA 分子 (sRNA) 进行。然而，对于毒力至关重要的 QseA 和 sRNA 基因调控的许多方面仍然知之甚少。该应用代表了探索 QseA 和负责 EHEC 毒力基因调控的 sRNA 功能的全面努力。具体目标是 (1) 确定 QseA 激活和抑制靶基因的机制，(2) 表征 QseA 在 EHEC 毒力基因调控中的作用，以及 (3) 阐明小 RNA (sRNA) 分子的作用EHEC 转录后基因调控。所提出的实验方法将更好地了解肠出血性大肠杆菌激活其毒力基因的机制，并可能揭示肠出血性大肠杆菌发病机制的潜在新方面。这些数据可能最终导致针对肠出血性大肠杆菌感染的独特治疗策略的开发。