Emerging understanding of the rat flea response to Yersinia pestis infection

对鼠蚤对鼠疫耶尔森氏菌感染反应的新认识

• 批准号: 10593692
• 负责人: Viveka Vadyvaloo
• 金额: $ 24.03万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-11 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593692
• 关键词: Acetylcysteine; Anatomy; Antioxidants; Area; Arthropods; Back; Bacteria; Biological Process; Biology; Blood; Chloroquine; Color; Communicable Diseases; Dermis; Development; Digestion; Disease; Disease Management; Drug Metabolic Detoxication; Environmental Impact; Event; Exhibits; Fleas; Gene Expression Profiling; Genes; Goals; Gram-Negative Bacteria; Health; Heme; Human; Immune; Immune response; In Situ Hybridization; Infection; Insecticide Resistance; Insecticides; Kinetics; Knowledge; Link; Lipids; Mediating; Microbial Biofilms; Mission; Mus; Oxidases; Oxygenases; Parasites; Pathology; Physiology; Plague; Polymers; Primitive foregut structure; Process; Production; Proliferating; Proventriculus; Public Health; Rattus; Reactive Oxygen Species; Research; Rickettsia Infections; Rodent; Role; Site; Source; Testing; Toxic effect; Toxin; Transcript; United States National Institutes of Health; Vector-transmitted infectious disease; Yersinia; Yersinia pestis; blood product; comparative; defense response; feeding; flea-borne; follow-up; hemozoin; human disease; mutant; novel; pathogen; pathogenic bacteria; polymerization; response; success; transcriptomics; transmission process; vector

PROJECT SUMMARY Fleas are obligate blood-feeding arthropods that are associated with several notable bacterial-derived human diseases, i.e. rickettsioses, bartonelloses, and plague. Plague caused by the Gram negative bacterium, Yersinia pestis, is difficult to eradicate because flea-borne transmission is endemic in natural foci of wild rodents and their associated fleas world-wide. Insecticide control is the primary strategy for disease management, but like many vector-borne diseases this is compromised by development of insecticide resistance in fleas. Development of novel vector-based strategies for bacterial pathogen control are therefore a priority. However, to accomplish this, we must overcome the dearth in knowledge regarding flea biology, particularly the detailed processes of the flea host response to infection. Towards this goal our lab has recently made novel observations that the Y. pestis factor Ymt is involved in manipulating the bloodmeal digestion processes related to detoxification of heme in a blood source dependent manner. Our goals are to understand the Ymt-mediated flea responses to infection that underlie successful Y. pestis infection of rat fleas. Therefore, our central hypothesis is that Ymt modulates mouse blood digestion processes related to heme detoxification and antioxidant defense to enable Y. pestis infection in rat fleas. Two aims will test this hypothesis. In Aim 1 we will determine if bloodmeal derived heme is correlated with flea ROS-mediated immune responses in a Ymt and blood source dependent manner. In Aim 2 we will use comparative transcriptomics to identify flea transcripts that are modulated in a Ymt-specific manner. Our proposed exploratory studies have potential to uncover biological processes related to blood digestion and immune processes in flea vectors that can be targeted to reduce establishment of transmissible infections to humans. Therefore, the proposed research lies within a part of the NIH's mission to develop fundamental knowledge that will assist in reducing the burden of infectious diseases on human health.

项目概要 跳蚤是专性吸血节肢动物，与几种著名的细菌衍生的人类有联系 疾病，即立克次体病、巴尔通体病和鼠疫。由革兰氏阴性菌耶尔森氏菌引起的鼠疫 鼠疫菌很难根除，因为跳蚤传播的传播在野生啮齿动物及其动物的自然疫源地中很普遍。 世界范围内的相关跳蚤。杀虫剂控制是疾病管理的主要策略，但与许多 媒介传播的疾病由于跳蚤对杀虫剂产生抗药性而受到损害。发展 因此，基于载体的新型细菌病原体控制策略是当务之急。然而，为了实现这一目标， 我们必须克服跳蚤生物学知识的匮乏，特别是跳蚤的详细过程 宿主对感染的反应。为了实现这一目标，我们的实验室最近做出了新的观察，即鼠疫耶尔森氏菌 因子 Ymt 参与操纵与血红素解毒相关的血粉消化过程。 血源依赖方式。我们的目标是了解 Ymt 介导的跳蚤对感染的反应 鼠蚤成功感染鼠疫耶尔森氏菌的基础。因此，我们的中心假设是 Ymt 调节小鼠 与血红素解毒和抗氧化防御相关的血液消化过程使鼠疫杆菌感染 老鼠跳蚤。有两个目标将检验这一假设。在目标 1 中，我们将确定血粉来源的血红素是否相关 跳蚤 ROS 介导的免疫反应以 Ymt 和血液来源依赖的方式进行。在目标 2 中我们将使用 比较转录组学，以确定以 Ymt 特异性方式调节的跳蚤转录本。我们的 拟议的探索性研究有可能揭示与血液消化和 跳蚤载体中的免疫过程可以减少传染性感染的发生 人类。因此，拟议的研究属于 NIH 开发基础药物使命的一部分。 有助于减轻传染病对人类健康负担的知识。