Mapping Protein Interactions between Filaria and its Wolbachia Endosymbiont

绘制丝虫与其沃尔巴克氏体内共生体之间的蛋白质相互作用

• 批准号: 7617551
• 负责人: THOMAS R UNNASCH
• 金额: $ 39.62万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617551
• 关键词: Adult; Affinity; Antibiotics; Bacteria; Bacteriophages; Binding; Binding Proteins; Biochemical Genetics; Bioinformatics; Biological; Biological Assay; Brugia malayi; Child; Communication; Communities; Country; Crude Extracts; Development; Disease; Doxycycline; Drug Delivery Systems; Drug usage; Economics; Elements; Enzyme-Linked Immunosorbent Assay; Exhibits; Female; Female sterility; Filariasis; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Human; Humanities; Hybrids; Individual; Infection; Insecta; International; Longevity; Maps; Metabolic; Methods; Molecular; Nuclear; Pan Genus; Parasites; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; Population; Process; Proteins; Proteomics; Public Health; RNA; Recombinants; Regulatory Element; Reproduction; Research; Resistance development; Screening procedure; Signal Pathway; Sterilization for infection control; Surface; System; Testing; Tetracyclines; Time; Transfection; Treatment Protocols; Wolbachia; Woman; Yeasts; cDNA Library; combat; filaria; genome wide association study; genome-wide analysis; killings; male; parasite genome; pregnant; pressure; programs; protein protein interaction; reproductive; response; tool; yeast two hybrid system

DESCRIPTION (provided by applicant): Filarial parasites afflict hundreds of millions of individuals worldwide, and represent significant public health problems in many of the poorest countries in the world. The currently available drugs used to combat these infections have several drawbacks, including the need for very long chemotherapeutic courses and the potential for the development of resistance. As a result, the development of new drugs to treat these infections is an important goal in the field of filariasis research. Most of the human filarial parasite species harbor an endosymbiotic bacterium of the genus Wolbachia. These endo-bacteria are essential, as elimination of the endosymbiont leads to sterilization of the adult female parasite. However, the antibiotic regimens that have been used to rid the parasites of the endosymbiont are of very long duration and require the use of a drug whose use is very limited. Thus, the need exists for the development of new chemotherapeutic approaches that can practically exploit the vulnerability of the human filarial parasites to the loss of the Wolbachia endosymbiont. Previous biochemical and genetic studies have established that communication between the host and Wolbachia endobacterium is essential for the Wolbachia to maintain itself and for it to spread throughout the host population. The overall goal of this proposal will be to identify the proteins that are involved in this endosymbiotic relationship and then to establish the functional networks of the genes involved in the process. The specific aims of the project are: 1. To map the interactome of the endosymbiont and its host. 2. To identify B. malayi nuclear-encoded genes involved in the endosymbiotic interaction. 3. To develop genetic regulatory and functional networks of parasite genes involved in the endosymbiotic relationship. The diseases caused by filarial parasites afflict hundreds of millions of individuals worldwide, and represent significant public health and socio-economic problems in many of the poorest countries in the world. Because of the public health importance of filarial infections, the international community has been supporting various filariasis control programs for over thirty years. The cumulative expenses of these programs now total in the hundreds of millions of dollars. However, progress in the elimination of the human filaria has been hampered by the paucity of efficient tools to combat these infections. The one tool that is really lacking is a method to kill or permanently sterilize the adult female parasites. Without such a tool, the control programs must maintain a high degree of pressure on the parasite population for the effective lifespan of the adult female parasite, a period which can extend to 12 years or more. Recent studies indicated that an intracellular bacterium in these parasites is essential for parasite reproduction and that elimination of this bacterium from the parasite results in sterility of the female worm. This program, if successful will suggest new drug targets that may be used to kill this bacterium, thereby sterilizing the female parasite and giving humanity a potent new tool to use against these parasites.

描述（由申请人提供）：丝状寄生虫困扰着全球数亿人，在世界上许多最贫穷的国家中代表着重大的公共卫生问题。目前用于对抗这些感染的药物有几个缺点，包括需要很长的化学治疗课程以及抗药性发展的潜力。结果，在治疗这些感染的新药物的开发是丝虫病研究领域的重要目标。大多数人类丝状寄生虫物种都有沃尔巴基亚属的内共生细菌。这些内部 - 细菌是必不可少的，因为消除了内共生菌会导致成年雌性寄生虫的灭菌。但是，已用于消除内共生体的寄生虫的抗生素方案的持续时间很长，需要使用使用非常有限的药物。因此，需要开发新的化学治疗方法的需求，这些方法实际上可以利用人类丝状寄生虫对沃尔巴基亚内共生体的丧失的脆弱性。先前的生化和遗传研究已经确定，宿主与沃尔巴奇内部杆菌之间的交流对于沃尔巴基亚维护自身并在整个宿主人群中传播至关重要。该建议的总体目标是确定与这种内共生关系有关的蛋白质，然后建立该过程中涉及的基因的功能网络。该项目的具体目的是：1。绘制内共生体及其宿主的相互作用。 2。鉴定马来语核编码基因涉及内共生相互作用。 3。开发涉及内共生关系的寄生虫基因的遗传调节和功能网络。丝状寄生虫引起的疾病困扰着全世界数亿人，在世界上许多最贫穷的国家中代表了重大的公共卫生和社会经济问题。由于丝状感染的公共卫生重要性，国际社会已经支持了三十多年的各种丝虫病控制计划。这些计划的累计支出现在总计数亿美元。然而，消除人丝虫的进展受到了对抗这些感染的有效工具的匮乏。真正缺少的一种工具是一种杀死或永久对成年女性寄生虫进行消毒的方法。没有这样的工具，控制计划必须在成年女性寄生虫的有效寿命中对寄生虫种群保持高度的压力，这一时期可以延长至12年或更长时间。最近的研究表明，这些寄生虫中的细胞内细菌对于寄生虫的繁殖至关重要，并且从寄生虫中消除这种细菌会导致雌性蠕虫的不育。如果成功的话，该程序将建议可能用于杀死该细菌的新药物靶标，从而对雌性寄生虫进行灭菌，并为人类提供一种有效的新工具，可以使用这些寄生虫。