Molecular Dissection of E. Histolytica Pathogenesis

溶组织内阿米巴发病机制的分子解剖

基本信息

批准号：
7167433
负责人：
SAMUEL L. STANLEY
金额：
$ 36.95万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-02-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7167433
关键词：
Acids Amebiasis Amebic Liver Abscess Amebic colitis Amoeba genus Animal Model Apoptosis Bacteria Binding Biological Biology Blood Circulation Blood-Borne Pathogens CHRM1 gene Caspase Gene Cells Colon Complement Complex Cysteine Protease Defensins Disease Disease model Dissection Endopeptidases Entamoeba histolytica Environment Epithelial Cells Equation Exhibits Extracellular Matrix Proteins Fermentation Fibronectins Food Functional disorder Funding Gal-GalNAc Gene Expression Gene Expression Profile Genes Genome Genus Cola Health Heat-Shock Response Host Defense Human Immune Immune response In Situ Individual Infection Inflammation Inflammatory Inflammatory Response Intestines Invaded Invasive Knowledge Lectin Link Liver Liver Abscess Mediating Mediator of activation protein Microscope Mitochondria Modeling Molecular Mucins Mucous Membrane Mus Nature Oligonucleotides Oxygen measurement, partial pressure, arterial PTGS2 gene Parasites Pathogenesis Pathway interactions Peptide Hydrolases Peptides Phagocytosis Physiological Play Positioning Attribute Production Progress Reports Public Health RNA Reagent Regulation Research Personnel Rest Role SCID Mice Side Signal Transduction Stimulus System Techniques Testing Therapeutic Tissues Transgenic Organisms Virulence Virulence Factors Virulent Volatile Fatty Acids Water Work Xenograft procedure antimicrobial base chemokine cytokine design extracellular free radical oxygen inhibitor/antagonist insight killings laser capture microdissection macromolecule macrophage mouse model neutrophil novel vaccines parasitism pathogen programs receptor research study response transcription factor

项目摘要

DESCRIPTION (provided by applicant): The protozoan parasite Entamoeba histolytica causes amebiasis, which remains a major health problem in much of the world, and is considered a potential biological weapon. The two main forms of disease, amebic colitis and amebic liver abscess arise from complex interactions between the host and parasite. In the previous funding period, we focused primarily on the host, and established new paradigms about the role of inflammation and apoptosis in amebic disease. In this renewal we will return our focus to the parasite, and will look at what we have termed the amebic virulence program: E. histolytica molecules that must be expressed or suppressed to allow amebic invasion and survival within host tissues. We will define the virulence program through a transcriptional analysis, and ask how the virulence repertoire differs between amebic trophozoites in culture, those that have invaded into the colonic mucosa, and trophozoites within the liver. We will attempt to identify the requisite components of this response, and determine whether blocking their expression can alter the course of amebic colitis or amebic liver abscess. We will test the hypothesis that host macromolecules serve as triggers for the activation of the amebic virulence program, and test candidate amebic molecules for their role in recognizing host molecules and initiating the amebic virulence program: We will then determine whether blocking host macromolecule recognition, or signaling by amebic receptors, alters the course of amebic colitis. The above studies look at virulence in the context of amebic response to the host. We will also investigate the inherent virulence repertoire of E. histolytica HM1:IMSS by looking at differences at the transcriptional level between HM1 :IMSS and the reduced virulence E. histolytica Rahman. When complete, these studies should provide new insights into the biology of E. histolytica, will further our understanding of the pathophysiology of amebic colitis and amebic liver abscess, and will identify new virulence factors that may play unique roles in amebic colitis or amebic liver abscess and could be targets for new vaccines or therapeutics.

描述（由申请人提供）：原生动物寄生虫溶组织内阿米巴引起阿米巴病，阿米巴病仍然是世界大部分地区的主要健康问题，并被认为是潜在的生物武器。阿米巴结肠炎和阿米巴肝脓肿这两种主要疾病形式是由宿主和寄生虫之间复杂的相互作用引起的。在之前的资助期间，我们主要关注宿主，并建立了关于炎症和细胞凋亡在阿米巴疾病中的作用的新范例。在本次更新中，我们将把注意力重新集中在寄生虫上，并将研究我们所说的阿米巴毒力程序：必须表达或抑制阿米巴分子才能允许阿米巴在宿主组织内入侵和生存。我们将通过转录分析来定义毒力程序，并询问培养物中的阿米巴滋养体、侵入结肠粘膜的滋养体和肝脏内的滋养体之间的毒力库有何不同。我们将尝试确定这种反应的必要组成部分，并确定阻断它们的表达是否可以改变阿米巴结肠炎或阿米巴肝脓肿的病程。我们将测试宿主大分子作为阿米巴毒力程序激活触发器的假设，并测试候选阿米巴分子在识别宿主分子和启动阿米巴毒力程序中的作用：然后我们将确定是否阻断宿主大分子识别，或阿米巴受体发出的信号，改变阿米巴结肠炎的病程。上述研究着眼于阿米巴对宿主反应的毒力。我们还将通过观察 HM1:IMSS 和毒力降低的溶组织内阿米巴 Rahman 之间转录水平的差异来研究溶组织内阿米巴 HM1:IMSS 的固有毒力。完成后，这些研究将为溶组织内阿米巴的生物学提供新的见解，将进一步加深我们对阿米巴结肠炎和阿米巴肝脓肿病理生理学的理解，并将确定可能在阿米巴结肠炎或阿米巴肝脓肿中发挥独特作用的新毒力因子并可能成为新疫苗或疗法的目标。