Yersinia pestis biofilms on C. elegans

线虫上的鼠疫耶尔森氏菌生物膜

• 批准号: 6820394
• 负责人: Creg Darby
• 金额: $ 29万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6820394
• 关键词: Caenorhabditis elegans; RNA interference; Yersinia pestis; Yersinia pestis disease; bacteria infection mechanism; bacterial genetics; bacterial proteins; biofilm; bioterrorism /chemical warfare; disease vectors; gene expression; green fluorescent proteins; host organism interaction; molecular cloning; polymerase chain reaction

DESCRIPTION (provided by applicant): The goal of this research is to understand the mechanism by which the bubonic plague bacterium, Yersinia pestis, colonizes its vector, the flea. This proposal describes an experimental system in which the nematode Caenorhabditis elegans is a surrogate for the flea, which allows use of powerful model organism genetic methods. Y. pestis colonizes the flea digestive tract and physically blocks the insect from feeding, leading to transmission of plague to new hosts through flea bites. This process requires the bacterial genes known as hms. Y. pestis creates a visible biofilm on the surface of C. elegans, which also requires hms genes. The biofilm blocks feeding of the nematodes and impairs their growth, a physical effect similar to the feeding blockage that occurs in the digestive tracts of infected fleas. These observations suggest that Y. pestis blocks fleas with a biofilm. The nematode will be used to further understand this process in an easily manipulated laboratory system, and the results can then be investigated directly in flea-bacteria interactions. The impact on human health of these studies will be: 1) Identification and characterization, in bacteria or flea or both, of molecular targets for drugs that could reduce or eliminate plague in rodent flea populations and be used in response to bioweapon attacks with plague-carrying fleas. 2) Deeper understanding of how biofilms attach to living tissues, a process important in a wide variety of infectious diseases. 3) Identification of nematode surface components, with potential for translation to treatment of helminthic infections. The specific aims of this proposal are: 1) Determine the roles in biofilm formation of hms and other Yersinia genes. 2) Determine the polysaccharide content and structure of the biofilm and develop reagents for its detection. 3) Clone three C. elegans gene involved in biofilm adherence and determine the localization in the worm of the encoded proteins.

描述（由申请人提供）：这项研究的目的是了解泡沫状鼠疫细菌，鼠疫耶尔森氏菌的机制，将其载体定居于其载体，跳蚤。该提案描述了一个实验系统，其中线虫秀丽隐杆线虫是跳蚤的替代物，它允许使用强大的模型生物遗传学方法。 Y. Pestis在跳蚤消化道上定居，并物理阻止昆虫的进食，从而通过跳蚤叮咬将瘟疫传播到新宿主。此过程需要称为HMS的细菌基因。 Y. Pestis在秀丽隐杆线虫的表面上产生可见的生物膜，这也需要HMS基因。生物膜阻塞了线虫的进食并损害其生长，这种物理作用类似于在感染跳蚤的消化道中发生的进食阻塞。这些观察结果表明Y. Pestis用生物膜阻塞跳蚤。线虫将用于在易于操纵的实验室系统中进一步了解这一过程，然后可以直接在跳蚤 - 细菌相互作用中研究结果。 这些研究对人类健康的影响将是：1）在细菌或跳蚤或两者兼有分子靶标的药物中鉴定和表征，这些药物可能会减少或消除啮齿动物跳蚤种群中的瘟疫，并用于响应生物妇女群和鼠疫携带的跳蚤的攻击。 2）更深入地了解生物膜如何附着在生物组织上，这一过程在各种传​​染病中很重要。 3）鉴定线虫表面成分，有可能转化为蠕虫感染的治疗。 该提案的具体目的是：1）确定在HMS和其他Yersinia基因的生物膜形成中的作用。 2）确定生物膜的多糖含量和结构，并开发用于检测的试剂。 3）克隆三甲虫基因与生物膜粘附有关，并确定编码蛋白蠕虫中的定位。