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: 7545685
• 负责人: Melissa Kendall
• 金额: $ 4.96万
• 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/7545685
• 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 O157; Gene Expression Regulation; Gene Targeting; Genes; Genus Cola; Hemolytic-Uremic Syndrome; Hormones; Hospitalization; Human; Infection; 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; gastrointestinal microvillus; mortality; novel; pathogen; quorum sensing; stem; transcription factor

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.

性状（由申请方提供）：肠出血性大肠杆菌。大肠杆菌（EHEC）O 157：H7在世界各地引起出血性腹泻和溶血性尿毒系统（HUS）。肠出血性大肠杆菌的感染剂量很低，因此很难进行流行病学控制。肠出血性大肠杆菌在大肠定植，引起附着和消退（AE）病变，并产生滋贺毒素，导致溶血性尿毒综合征的主要症状。每年，仅在美国，肠出血性大肠杆菌就造成7万多人患病，2000人住院，7万人死亡。肠出血性大肠杆菌可感受到正常胃肠道植物群产生的细菌自身诱导物（AI-3），以及宿主产生的肾上腺素和去甲肾上腺素激素，从而激活其毒力基因的表达。毒力基因的其他调节通过转录因子QseA和小RNA分子（sRNA）发生。然而，关于QseA和sRNA基因调控的许多方面，这是至关重要的毒力，仍然知之甚少。该应用代表了探索QseA和负责肠出血性大肠杆菌毒力基因调控的sRNA的功能的全面努力。目的：（1）明确QseA激活和抑制靶基因的机制;（2）研究QseA在EHEC毒力基因调控中的作用;（3）阐明小RNA（small RNA，sRNA）分子在EHEC转录后基因调控中的作用。所提出的实验方法将实现更好地了解EHEC激活其毒力基因的机制，并可能揭示EHEC发病机制的新方面。这些数据可能最终导致EHEC感染的独特治疗策略的发展。