How Bacteria Colonize Ticks: The Role of Antimicrobial Peptides

细菌如何定植蜱虫：抗菌肽的作用

• 批准号: 0212901
• 负责人: Wayne Hynes
• 金额: --
• 依托单位: Old Dominion University Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-10-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0212901&HistoricalAwards=false
• 关键词: How; Bacteria; Colonize; Ticks; Role

Ticks are vectors of a number of important diseases, and with mechanisms for controlling ticks often less effective than those for controlling insects, these arachnids may be more of a health problem for humans and wildlife than insects. The long term goals of the these studies are to aid in the development of mechanisms for preventing transmission of disease-causing microbes from the tick to its next host, and to exploit differences between tick genera to develop control measures for the spread of infectious diseases or to control the microorganisms themselves.This study addresses the fundamental issue of the tick response to bacterial infection and also addresses the question of why some microbes have been able to successfully colonize blood-feeding arthropods and become the agents of vector-borne diseases. Specifically the proposal examines the hypothesis that Dermacentor variabilis (American dog tick) expresses a robust antimicrobial response following bacterial challenge. In contrast Ixodes scapularis (deer tick) and Amblyomma americanum (Lone Star tick) do not appear to express this response, at least to the same microbes. The proposed studies will provide information on how and why these ticks respond differently to assorted microbes. This project will concentrate on one fundamental mechanism by which blood-feeding arthropods resist infection by invading microbes. This is the use of antimicrobial peptides, in particular the defensins, a key component of an organism's innate immune response. The project will use ticks because they harbor and transmit a greater variety of microbes than any other arthropod group. Many arthropods possess a well-developed immune system that rejects most invading microbes, however, little is known about the immune system in ticks. More precise knowledge is needed to understand the limitations in the tick's immune system that have encouraged the ability to harbor such a variety of microorganisms. Ticks of the genus Ixodes tolerate a greater diversity of microbial species than other tick genera. Other genera, including Dermacentor and Amblyomma are noted for their association with one, or at most two specific types of microbe. Most Ixodes spp. that are microbe-tolerant are generalists, feeding on a diverse array of hosts ranging from cold-blooded vertebrates to almost any type of bird or mammal. It is proposed that these tick generalists have a less efficient immune system that facilitates colonization by a diverse array of invading microbes. It is hypothesized that differences in the tick innate immune mechanisms are important determinants of their ability to function as vectors of pathogenic agents. By using the Lyme disease-causing spirochete Borrelia burgdorferi, and a non-pathogenic bacterium, Rickettsia montana, and comparing the response to these microbes in Ixodes scapularis (the vector for B. burgdorferi), Dermacentor variabilis (host for R. montana) and Amblyomma americanum (vector for Ehrlichia), the role of defensin will be examined. The hypothesis will be explored within four aims, concentrating on the tick defensin, varisin. The aims are: (1) Characterize the tick defensin gene (vsnD) from D. variabilis. (2) Determine in which tissues of the adult tick the varisin gene is expressed, and whether the defensin is expressed by nymphs, perhaps giving an indication that defensin is important throughout the various life stages of the tick. (3) Determine whether other tick genera (Ixodes and Amblyomma) have and selectively express a defensin gene in response to different bacteria. (4) Compare the response of the different ticks to Rickettsia montana, an intracellular organism normally found in D. variabilis. Results of these studies will improve our understanding of the role of defensin in the innate immune response of ticks following challenge with various microbes. Elucidation of this critically important defensive system will provide information regarding the reason some of these ticks transmit disease-causing microorganisms.

蜱虫是许多重要疾病的媒介，控制蜱虫的机制往往不如控制昆虫的机制有效，这些蜘蛛可能比昆虫更能给人类和野生动物带来健康问题。这些研究的长期目标是帮助开发防止致病微生物从蜱虫传播到下一个宿主的机制，并利用蜱属之间的差异来制定控制传染病传播的措施或控制微生物本身。这项研究解决了蜱对细菌感染的反应的基本问题，也解决了为什么有些微生物能够成功地在吸血节肢动物体内定植，成为病媒传播疾病的媒介。具体而言，该提案检查了变异革蜱（美国犬蜱）在细菌挑战后表达强大的抗菌反应的假设。相反，肩胛硬蜱（鹿蜱）和美洲钝眼蜱（孤星星蜱）似乎不表达这种反应，至少对相同的微生物。拟议的研究将提供有关这些蜱虫如何以及为什么对各种微生物有不同反应的信息。这个项目将集中在一个基本的机制，其中吸血节肢动物抵抗入侵的微生物感染。这是使用抗菌肽，特别是防御素，生物体先天免疫反应的关键组成部分。该项目将使用蜱虫，因为它们比任何其他节肢动物群体都携带和传播更多种类的微生物。许多节肢动物具有发达的免疫系统，可以拒绝大多数入侵微生物，然而，对蜱的免疫系统知之甚少。需要更精确的知识来了解蜱虫免疫系统的局限性，这些局限性鼓励了这种窝藏各种微生物的能力。硬蜱属的蜱比其他蜱属耐受更大的微生物物种多样性。其他属，包括革蜱属和钝眼蜱属，因其与一种或最多两种特定类型的微生物有关而闻名。 大多数硬蜱属对微生物有耐受力的动物是多面手，以各种各样的宿主为食，从冷血脊椎动物到几乎任何类型的鸟类或哺乳动物。 有人提出，这些蜱类通才具有效率较低的免疫系统，有利于各种入侵微生物的定植。据推测，蜱固有免疫机制的差异是其作为病原体载体的能力的重要决定因素。通过使用莱姆病致病螺旋体伯氏疏螺旋体和非致病性细菌蒙大拿立克次体，并比较肩突硬蜱（B的载体）对这些微生物的反应。burgdorferi）、变异革蜱Dermacentor variabilis（寄主为革蜱R. montana）和Amblyomma americanum（埃里希体的载体）中，将检验防御素的作用。该假说将探讨在四个目标，集中在蜱防御素，varisin。目的是：（1）鉴定蜱防御素基因（vsnD）。变异性。(2)确定varisin基因在成年蜱的哪些组织中表达，以及防御素是否在蜱中表达，这可能表明防御素在蜱的各个生命阶段都很重要。(3)确定其他蜱属（硬蜱属和钝眼蜱属）是否具有并选择性表达防御素基因以应对不同的细菌。(4)比较不同蜱对山地立克次体的反应，山地立克次体是一种通常在D.变量这些研究的结果将提高我们对防御素在各种微生物攻击后蜱的先天免疫应答中的作用的理解。阐明这一至关重要的防御系统将提供有关这些蜱传播致病微生物的原因的信息。