Molecular dynamics of rickettsial infection in ticks

蜱立克次体感染的分子动力学

• 批准号: 7028919
• 负责人: Kevin R. Macaluso
• 金额: $ 10.8万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7028919
• 关键词: Ixodes; Rickettsia rickettsii; Rocky Mountain spotted fever; antibody; bacteria infection mechanism; bacterial genetics; cell surface receptors; complementary DNA; cytoskeleton; differential display technique; gene expression; genetic library; green fluorescent proteins; host organism interaction; molecular dynamics; nucleic acid sequence; polymerase chain reaction; recombinant proteins

DESCRIPTION (provided by applicant): Rocky Mountain spotted fever is the most frequently reported rickettsial disease in the United States. The etiologic agent, Rickettsia rickettsii, of this potentially fatal disease is transmitted to humans by the bite of infected ixodid ticks. Although, tick-transmitted spotted fever group (SFG) rickettsiae are maintained effectively in nature via transovarial transmission, very little is known about the molecular basis underlying rickettsial maintenance in ticks. The mechanisms by which rickettsiae propagate in tick tissues and their interaction with host tissues, including salivary glands, gut, and the ovaries are critical for our understanding of rickettsiae-tick interactions. Preliminary studies demonstrated that ticks and rickettsiae exist in a relationship in which the tick actively responds to the infecting rickettsiae. Although candidate molecules involved in this response have been identified, the extent to which rickettsiae interact with these tick-derived molecules is not known. Therefore, the goal of this proposal is to further determine the degree of interaction between SFG rickettsiae and ticks through molecular and functional characterization assays. Based on DNA sequence comparisons, candidate molecules putatively identified as membrane receptors (clathrin-coated VATPase, E-selectin precursor, GPV-CD42D) and cytoskeletal (VASP, alpha-catenin, and alpha-tubulin) components will be assessed for their utilization by rickettsiae. Recombinant proteins will be generated for selected candidate molecules and tested for interaction with rickettsiae by adhesion/invasion assays and GFP-reporter fusion protein utilization assays. These studies will further our understanding of both tick physiology and rickettsial transmission.

描述（由申请人提供）：落基山斑疹热是美国最常报告的立克次体病。这种潜在致命疾病的病原体立克次氏体通过受感染的硬蜱叮咬传播给人类。虽然，蜱传斑点热群（SFG）立克次体通过跨卵传播在自然界中有效地维持，但对蜱中立克次体维持的分子基础知之甚少。立克次体在蜱组织中传播的机制及其与宿主组织（包括唾液腺、肠道和卵巢）的相互作用对于我们理解立克次体-蜱相互作用至关重要。初步研究表明，蜱和立克次体存在一种关系，其中蜱对感染立克次体有积极反应。虽然参与这种反应的候选分子已经被确定，但立克次体与这些蜱源分子相互作用的程度尚不清楚。因此，本提案的目标是通过分子和功能表征分析进一步确定SFG立克次体与蜱之间的相互作用程度。基于DNA序列比较，将评估鉴定为膜受体（网格蛋白包被的VATP酶、E-选择素前体、GPV-CD 42 D）和细胞骨架（VASP、α-连环蛋白和α-微管蛋白）组分的候选分子puristic是否被立克次体利用。将为选定的候选分子生成重组蛋白，并通过粘附/侵袭试验和GFP-报告融合蛋白利用试验检测与立克次体的相互作用。这些研究将进一步加深我们对蜱生理学和立克次体传播的理解。

项目成果

Characterization and growth of polymorphic Rickettsia felis in a tick cell line.

蜱细胞系中多态性猫立克次体的表征和生长。

• DOI: 10.1128/aem.00025-08
• 发表时间: 2008
• 期刊: Applied and environmental microbiology
• 影响因子: 4.4
• 作者: Sunyakumthorn,Piyanate;Bourchookarn,Apichai;Pornwiroon,Walairat;David,Connie;Barker,StevenA;Macaluso,KevinR
• 通讯作者: Macaluso,KevinR