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Metabolic interdependency of tsetse fly symbiosis

采采蝇共生代谢的相互依赖性

基本信息

批准号：
8072084
负责人：
Rita V M Rio
金额：
$ 7.25万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-15 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8072084
关键词：
ATP-Binding Cassette Transporters Adult African Trypanosomiasis Agriculture Amino Acids Biology Blood Cell Proliferation Competence Data Development Digestion Enteral Exhibits Fertility Gastrointestinal tract structure Gene Expression Genetic Recombination Goals Growth Homeostasis In Vitro Individual Infection Knock-out Knowledge Life Life Style Lipids Longevity Metabolic Midgut Molecular Mutagenesis Nutritional status Pathway interactions Phenotype Process Public Health Regulation Research Role Source Specificity Staging Supplementation Symbiosis Testing Thiamine Time Tissues Trypanosoma brucei brucei Tsetse Flies Vitamin B Complex Vitamins Wigglesworthia Wigglesworthia glossinidia Wolbachia base combat comparative genomics cost density feeding fitness fly genetic manipulation microbial microbial community mutant mutualism novel parasitism public health relevance reconstitution reproductive socioeconomics trait transmission process vector vector control

项目摘要

DESCRIPTION (provided by applicant): The tsetse fly is of high public health and agricultural significance due to its obligate vector role in the transmission of African trypanosomiasis. Trypanosomes (Trypanosoma brucei subspp.) rely on the tsetse fly for their development, recombination, multiplication and transmission. Tsetse flies also harbour two enteric bacterial symbionts, Wigglesworthia glossinidia and Sodalis glossinidius. It is believed that these microbial symbionts provide metabolic capabilities that enable tsetse's specialized lifestyle of exclusive blood feeding. Blood although rich in amino acids and lipids is deficient in many B vitamins, particularly thiamine. The overall objective of the current proposal is to examine symbiotic metabolic integration and its role in tsetse fly fitness and vector competence. The specific hypothesis behind the proposed research is that energy processing by Sodalis and Wigglesworthia serves as a critical factor in the microbial homeostasis of the tsetse fly with disruption altering host fitness and vector competence. This hypothesis is based on the following observations. First, the similar growth dynamics of Sodalis and Wigglesworthia during metabolically intensive periods of tsetse development supports overlapping roles in energy processing. Second, significant Wigglesworthia and Sodalis proliferation occurs at the teneral adult (i.e. newly eclosed) life stage, the developmental period of highest vector competence in wild type tsetse flies. Third, comparative genomic analyses as well as their physical proximity within the tsetse midgut, suggests that de novo thiamine (Vitamin B1) synthesis is exclusively performed by Wigglesworthia and subsequently acquired by Sodalis through a thiamine salvage pathway. Fourth, our preliminary data demonstrate that the proliferation of Sodalis density requires vitamins provided by an exogenous source. Fifth, our preliminary data also suggests that the Sodalis thiamine salvage pathway is inversely regulated by exogenous sources of thiamine, specifically thiamine monophosphate (TMP), both in culture and within the tsetse fly. To test our hypothesis, the functional regulation of the Sodalis thiamine salvage pathway will be examined through expression analyses and genetic manipulation. Tsetse flies, Glossina morsitans morsitans, will be reconstituted with Sodalis thiamine recruitment mutants and host fitness traits evaluated. Lastly, the effect of B-vitamin supplementation towards reducing the higher vector competence exhibited by non-teneral Wigglesworthia-free tsetse flies will be investigated. A greater understanding of the energy processing of tsetse fly symbionts expands our existing knowledge of tsetse fly biology and may stimulate alternative strategies towards combating African trypanosomiasis. PUBLIC HEALTH RELEVANCE: The tsetse fly is of high public health and agricultural significance due to its vector role in the transmission of African trypanosomiasis. Tsetse flies also harbour a limited digestive tract microbial community that are critical components of their host's biology and also co-localize with trypanosome infections. The proposed research expands our understanding of tsetse fly biology and offers potential novel avenues for vector control strategies.

描述（由申请人提供）：采采蝇在非洲锥虫病的传播中扮演着重要的媒介角色，因此具有很高的公共卫生和农业意义。锥虫（布鲁氏锥虫亚种）依靠采采蝇进行发育、重组、繁殖和传播。采采蝇也有两种肠道细菌共生体，Wigglesworthia舌蝇和Sodalis舌蝇。据信，这些微生物共生体提供了代谢能力，使采采蝇能够专门以血液为食的生活方式。血液虽然富含氨基酸和脂质，但缺乏许多B族维生素，尤其是硫胺素。当前提案的总体目标是研究共生代谢整合及其在采采蝇适应性和媒介能力中的作用。提出的研究背后的具体假设是，Sodalis和Wigglesworthia的能量处理是采采蝇微生物稳态的关键因素，破坏了宿主的适应性和媒介能力。这一假设是基于以下观察。首先，Sodalis和Wigglesworthia在采采发育的代谢密集期有着相似的生长动态，这支持了它们在能量加工中的重叠作用。第二，在野生型采采蝇媒介能力最高的一般成虫（即新闭）发育阶段，Wigglesworthia和Sodalis增殖显著。第三，比较基因组分析以及它们在采采中肠内的物理接近性表明，从头合成硫胺素（维生素B1）完全由Wigglesworthia完成，随后由Sodalis通过硫胺素回收途径获得。第四，我们的初步数据表明，Sodalis密度的增殖需要外源提供的维生素。第五，我们的初步数据还表明，无论是在培养中还是在采采蝇体内，Sodalis硫胺素回收途径都受到外源硫胺素，特别是单磷酸硫胺素（TMP）的反向调节。为了验证我们的假设，我们将通过表达分析和基因操作来检查Sodalis硫胺素挽救途径的功能调控。用Sodalis硫胺素招募突变体对采采蝇（Glossina morsitans morsitans）进行重组，并对寄主的适合度性状进行评价。最后，将研究补充b族维生素对降低非无wigglesworthia采采蝇表现出的较高媒介能力的影响。对采采蝇共生体能量处理的更深入了解扩展了我们对采采蝇生物学的现有知识，并可能激发对抗非洲锥虫病的替代策略。