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Anaplasma phagocytophilum modulate tick gene expression for its survival and transmission from the vector host

嗜吞噬细胞无形体调节蜱基因表达以使其存活并从载体宿主传播

基本信息

批准号：
9398343
负责人：
Girish Neelakanta
金额：
$ 38.75万
依托单位：
OLD DOMINION UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-18 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9398343
关键词：
Actins Address Adult Affect Anaplasma phagocytophilum Antibodies Antifreeze Area Arthropod Vectors Arthropods Bacteria Binding Biochemical Biological Assay Biology Black-legged Tick Bovine Anaplasmosis Cells Confocal Microscopy Data Development Disease EMSA Electrophoretic Mobility Shift Assay Enzymes Female Gene Expression Genes Goals Human Immunization In Vitro Interruption Kynurenine-oxoglutarate aminotransferase Lead Mammalian Cell Mammals Medical Microbe Modeling Molecular Molecular Analysis Neuromodulator OATP Transporters Oxidative Stress Pathway interactions Phosphorylation Promoter Regions RNA Interference Regulation Reproduction Research Rickettsia Rickettsiales Role Salivary Glands Signal Pathway Signal Transduction Tick-Borne Diseases Ticks Tryptophan Tryptophan Metabolism Pathway United States Vertebrates Xanthurenic Acid base design egg experimental study field study in vivo insight knock-down male mouse model neutrophil novel pathogen transmission process vector vector transmission

项目摘要

Project Summary/Abstract Human anaplasmosis, caused by the obligate intracellular bacterium Anaplasma phagocytophilum, is one of the most common tick-borne diseases in the United States. In mammals and ticks, A. phagocytophilum resides in neutrophils and in salivary glands, respectively. Despite numerous studies that have focused on understanding strategies that A. phagocytophilum uses to survive in the mammalian cells, relatively few studies have clearly defined the molecular strategies that A. phagocytophilum uses to survive in ticks. In this project, we will be performing a comprehensive molecular analysis on Ixodes scapularis organic anion transporting polypeptides (OATPs) and genes involved in the tryptophan metabolism pathway in A. phagocytophilum-tick interactions. This study is build upon our efforts in showing how A. phagocytophilum modulates gene expression and cell signaling for its survival in the vector. As an example, our previous studies has shown that A. phagocytophilum modulate tick antifreeze gene expression and actin phosphorylation for its survival in the vector. Here, we provide strong preliminary in vitro and in vivo data showing that A. phagocytophilum induces expression of a specific OATP (OATP4056) and kynurenine aminotransferase (KAT), a gene involved in the tryptophan pathway. We now hypothesize that interplay between OATP4056 and KAT not only facilitates A. phagocytophilum survival in the vector but also aid in the transmission of this bacterium to a vertebrate host. RNAi analysis revealed that knockdown of OATP4056 has no effect on A. phagocytophilum acquisition but affected its survival and transmission from these ticks. Electrophoretic mobility shift assays with promoter region and total lysates prepared from uninfected and A. phagocytophilum-infected ticks provide further evidence that the presence of this bacterium influences expression of OATP4056 in these ticks. In addition, we found evidence that a metabolite from tryptophan pathway regulates A. phagocytophilum survival and OATP4056 gene expression in these ticks. These results provide important insights for our proposed studies to define molecular basis of the relationship of A. phagocytophilum with ticks. Based on our strong preliminary results and the experiments proposed, we believe that this could be a transformative study that not only serves as a model to study intimate relationships established by pathogens with their arthropod vectors but may also lead in the development of new strategies to interrupt the transmission of this and perhaps other Rickettsial species of medical importance.

项目总结/文摘