Identifying Borrelia turicatae genes needed for colonization and transmission fro

鉴定Borrelia turicatae定植和传播所需的基因

• 批准号: 8418749
• 负责人: Job E Lopez
• 金额: $ 10.8万
• 依托单位: MISSISSIPPI STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8418749
• 关键词: Address; Affect; Arthropod Vectors; Biological; Biology; Black-legged Tick; Blood; Blood-Borne Pathogens; Borrelia; Borrelia turicatae; Code; Country; Data; Developing Countries; Development; Disease; Enabling Factors; Gene Deletion; Gene Expression Profile; Gene Expression Regulation; Gene Family; Gene Silencing; Genes; Genetic; Genetic Determinism; Goals; Human; Human body; In Vitro; Infection; Laboratories; Left; Life Cycle Stages; Longevity; Lyme Disease; Mammals; Membrane Proteins; Modeling; Modification; Molecular; Morbidity - disease rate; Mus; Names; Order Spirochaetales; Ornithodoros; Pediculus humanus humanus; Plasmids; Proteins; Relapsing Fever; Resources; Rocky Mountain Spotted Fever; Role; System; Testing; Tick Control; Tick-Borne Diseases; Ticks; Time; Up-Regulation; base; density; disease transmission; feeding; gene complementation; global health; immunogenic; improved; mortality; novel strategies; novel therapeutics; pathogen; prevent; therapeutic development; transmission process; vector

DESCRIPTION (provided by applicant): Relapsing fever spirochetosis is a global disease transmitted by argasid (soft-shelled) ticks or the human body louse. Throughout the world, this disease causes severe morbidity and mortality if left untreated, primarily affecting those in resource poor countries. However, little is known regarding the molecular mechanisms involved with transmission of the spirochetes from the tick vector to the vertebrate host. Therefore, to address NIAID's role in improving global health, my goal for this proposal is to identify the genetic factors that enable a species of relapsing fever spirochetes, Borrelia turicatae, to colonize the tick and to be subsequently transmitted to the mammalian host. Furthermore, there are several distinctions between B. turicatae and Lyme disease-causing spirochetes which make B. turicatae advantageous for studying spirochete-host interactions. These differences include plasmid stability and retention of infectivity after prolonged in vitro cultivation, and the ability to reach high bacterial densities in mammalian blood. These distinctions have aided in the development of the proposed studies focusing on determining the necessity of outer membrane proteins (Omps) during tick colonization and transmission of B. turicatae from its tick vector, Ornithodoros turicata. The importance of a family of genes which code for Omps has been established in a different species of relapsing fever spirochetes, Borrelia hermsii. However, little is known about the role of Omps in other species that cause disease. Therefore, I propose to identify genes which code for Omps that are up-regulated within B. turicatae during tick infection. A microarray based approach will be used to identify these genetic determinants, and their necessity for tick colonization and transmission to the mammal will be determined. To accomplish this, I have developed the first system in B. turicatae for gene inactivation and complementation, and have established the only known laboratory tick colony for these studies. These findings will have a broad impact enabling the development of therapeutics blocking transmission of this disease, and will increase our understanding of the adaptation and transmission mechanisms of vector-borne pathogens.

描述（由申请人提供）：复发发烧螺旋病是一种由Argasid（软壳）tick虫或人体虱子传播的全球疾病。在世界范围内，如果不加以治疗，这种疾病会导致严重的发病率和死亡率，主要影响资源贫困国家的人。然而，关于与螺旋体从tick矢量传播到脊椎动物宿主有关的分子机制知之甚少。因此，为了解决NIAID在改善全球健康中的作用，我的这一提议的目标是确定能够使复发性发烧螺旋体（Borrelia turicatae）造成的遗传因素，以殖民tick虫并随后将其传播给哺乳动物宿主。此外，曲霉和引起莱姆病的螺旋体之间存在几个区别，这使得B. thericatae具有研究螺旋体宿主相互作用有利。这些差异包括延长体外培养后的质粒稳定性和感染性的保留，以及在哺乳动物血液中达到高细菌密度的能力。这些区别有助于开发拟议的研究，重点是确定在tick裂中的tick裂和传播中，从其tick vector tick载体ornithodoros turicata在壁虱定植和传播过程中的必要性。在不同种类的复发性发烧螺旋体Borrelia Hermsii中确定了一个基因家族的重要性。然而，关于OMP在引起疾病的其他物种中的作用知之甚少。因此，我建议确定在tick感染期间在曲霉内上调的OMPS代码的基因。将使用基于微阵列的方法来识别这些遗传决定因素，将确定它们的滴答殖民化和向哺乳动物传播的必要性。为此，我开发了用于基因失活和互补的B. turicatae中的第一个系统，并确立了这些研究的唯一已知的实验室壁虱菌落。这些发现将产生广泛的影响，从而能够开发这种疾病的治疗疗法的传播，并会增加我们对载体传播病原体的适应和传播机制的理解。