Phenotype MicroArray Analysis of Fastidious Pathogens

挑剔病原体的表型微阵列分析

基本信息

批准号：
7273799
负责人：
BARRY RONALD BOCHNER
金额：
$ 47.08万
依托单位：
BIOLOG, INC.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7273799
关键词：
Acquired Immunodeficiency Syndrome Aerobic Aerobic Bacteria Affect Anaerobic Bacteria Animal Model Antibiotic-Associated Colitis Arcobacter Area Autoimmune Process Bacteria Bacteroides Bacteroides thetaiotaomicron Biology Bioterrorism Campylobacter Campylobacter jejuni Cause of Death Cell Line Cessation of life Clostridium Clostridium difficile Collaborations Collection Colon Communicable Diseases Crohn&apos s disease Cutaneous Databases Development Diagnostic Diarrhea Disease Disease Association Drug resistance Escherichia Escherichia coli Evolution Food Gastroenteritis Genes Genome Genus Cola Genus Mycobacterium Geographic state Goals Guillain-Barré Syndrome Health Helicobacter Helicobacter pylori Homologous Gene Hospitals Human Immunocompromised Host Infection Intestines Investigation Knock-out Laboratories Lactobacillus Legionella Leprosy Lung Maduromycosis Metabolic Metabolic Pathway Metabolism Microarray Analysis Modeling Molecular Biology Techniques Monitor Moraxella Mycobacterium Infections Mycobacterium tuberculosis Neisseria Nerve Degeneration Nocardia Nocardia Infections Numbers Paralysed Paratuberculosis Peptic Ulcer Peripheral Nerves Pharmacotherapy Pharmacy facility Phase Phenotype Physiological Physiology Population Population Genetics Probiotics Production Property Protocols documentation Pseudomembranous Colitis Public Health Publications Range Research Research Personnel Rhodococcus Scanning Scientist Side Small Business Technology Transfer Research Stomach System Technology Technology Transfer Testing Texas Tissues Toxic Shock Syndrome Toxicology Universities Vagina Virulence Washington Wolinella Work World Health Organization antimicrobial drug biodefense college commercialization drug development expectation gene function genome sequencing human disease instrument interest knockout gene malignant stomach neoplasm member microbial microorganism mutant mycobacterial pathogen prevent research study resistance mechanism success tool

项目摘要

DESCRIPTION (provided by applicant): Mycobacterium tuberculosis and other Mycobacterium species are major pathogens around the world. They are part of a larger group of so-called fastidious pathogens that are difficult to study because, for a wide range of reasons, they are difficult to culture. Phenotype MicroArrayTM (PM) technology is a tool that can aid in understanding the physiological and metabolic properties of fastidious pathogens. It enables a scientist to scan nearly 2,000 phenotypes of a microbial cell line in a single experiment. This technology can now be used with most aerobic gram negative/positive species of interest in human health and more than 70 scientific publications and presentations demonstrate how it can be applied in a wide range of scientific investigations. However, a number of fastidious genera are currently not amenable to PM analysis. One principal goal for this STTR project is to adapt PM technology for these fastidious aerobic, microaerophilic, and anaerobic bacterial species, with special emphasis on those important in human disease and/or biodefense considerations. The genera we will focus on include agents of lung, cutaneous, and tissue infections (Mycobacterium, Nocardia, Legionella), microaerophilic gastro-intestinal pathogens (Helicobacter, Campylobacter, Arcobacter, Wolinella), and important colonizers of the colon and vagina (Bacteroides, Clostridium, Lactobacillus, Escherichia). These were selected as highest priority because we have received requests from more than 40 scientists seeking to utilize PM technology in their studies of these microorganisms. This level of scientific interest documents the need and potential for commercialization of the technology that we are proposing to develop. A second goal is to expand the capabilities of the Biolog Microbial Identification System, which is now installed in about half of US State Public Health Labs and is frequently used to identify less common or unusual microbial pathogens. Most of these genera are also not currently included in Biolog's Identification Database. However, with success in development efforts proposed here, the Database will be expanded to include these important fastidious species. As a third goal, our collaborator at Texas A&M University will focus on the most important genus, Mycobacterium, and use knockout strains with PM technology to study the function of genes that are unique to the metabolism and drug resistance of this genus. If successful, this aspect of the project will aid efforts toward the development of new or more effective anti-mycobacterial drug therapies. This project will directly benefit public health by providing a technology for efficient simultaneous testing of hundreds to thousands of cellular phenotypes. It will be applied in hospital diagnostic work, environmental diagnostic work, bioterrorism monitoring, new drug development, toxicology studies, and in many areas of basic biology research.

描述（由申请人提供）：结核分枝杆菌和其他分枝杆菌是世界各地的主要病原体。它们是一群很难研究的所谓挑剔的病原体的一部分，因为出于多种原因，它们很难培养。表型微阵列（PM）技术是一种工具，可以帮助理解挑剔的病原体的生理和代谢特性。它使科学家可以在一个实验中扫描近2,000个微生物细胞系的表型。现在，该技术可以与大多数有氧革兰氏阴性/积极物种对人类健康的兴趣一起使用，并且有70多种科学出版物和演示证明了如何将其应用于广泛的科学研究中。但是，目前不适合进行PM分析的许多挑剔的属。该STTR项目的一个主要目标是适应PM技术，以适应这些挑剔的有氧，微型粒细胞和厌氧细菌物种，并特别强调了在人类疾病和/或生物疾病方面重要的因素。我们将重点关注的属包括肺，皮肤和组织感染的药物（分枝杆菌，诺卡氏菌，军团菌），微粒细胞性胃肠道病原体（甲基杆菌，弯曲杆菌，弯曲杆菌，arcobacter，arcobobacter，wolinella），以及结肠和阴道的重要共同体（colline）（cobobacter）（埃切里希菌）。这些被选择为优先级，因为我们收到了40多位寻求利用PM技术的科学家的要求，以研究这些微生物。这种科学兴趣水平记录了我们建议开发的技术的商业化的需求和潜力。第二个目标是扩大生物微生物识别系统的功能，该系统现已安装在美国大约一半的州公共卫生实验室中，并经常用于识别较不常见或不寻常的微生物病原体。这些属中的大多数当前也未包含在生物学标识数据库中。但是，随着此处提出的开发工作的成功，数据库将扩展到包括这些重要的物种。作为第三个目标，我们在得克萨斯州A＆M大学的合作者将重点关注最重要的属，分枝杆菌，并将基因敲除菌株与PM技术一起研究该属的代谢和耐药性所独有的基因功能。如果成功的话，该项目的这一方面将有助于开发新的或更有效的抗菌药物疗法。该项目将通过提供有效同时测试数百至数千种细胞表型的技术来直接受益于公共卫生。它将应用于医院诊断工作，环境诊断工作，生物恐怖主义监测，新药物开发，毒理学研究以及基础生物学研究的许多领域。