Characterizing the Pan-genome of a Rickettsia Infecting the Eastern Black-legged Tick

感染东部黑腿蜱的立克次体的全基因组特征

基本信息

批准号：
10331878
负责人：
Timothy P Driscoll
金额：
$ 19.14万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-22 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331878
关键词：
Abbreviations Address Adult Alleles Anaplasma phagocytophilum Anaplasmosis Antibiotics Area Arthropods Babesia Babesiosis Bacteria Biology Biotin Black-legged Tick Borrelia Cell Line Cells Characteristics Chromosomes Communicable Diseases Data Disease Disease Vectors Distant Elements Evaluation Flavivirus Frequencies Future Gene Expression Genes Genetic Variation Genome Genomics Geography Goals Health Horizontal Gene Transfer Human Infection Inherited Life Style Lyme Disease Maintenance Mediating Metabolic Microbe Mobile Genetic Elements Names Nature Nutrient Nymph Parasites Pathogenesis Pathogenicity Peptide Synthesis Population Powassan virus Prevalence Process Proteins Pseudogenes Research Resistance Resolution Resources Rickettsia Rickettsia rickettsii Rocky Mountain Spotted Fever Role STEM research Shapes Specialist Testing Theileria Theileriasis Tick-Borne Diseases Ticks United States Vertebrates Work combat contig deep sequencing design endosymbiont experimental study feeding genetic element genetic variant genomic variation host microbiota human disease human pathogen infection rate innovation insight microbial novel pan-genome parasitism pathogen reference genome reproductive spreading factor superinfection tick population tick-borne tool transcriptome sequencing vector transmission vector-borne pathogen

项目摘要

PROJECT SUMMARY Microbial residents of arthropod disease vectors engender profound effects on the biology of their host, both positive (e.g., nutrient acquisition, defense from pathogens) and negative (e.g., reproductive parasitism). The mechanisms that underpin these microbial processes arise as evolutionary consequences of genetic variation and are often mediated by mobile genetic elements (MGEs). Even when these resident microbes are not known to be pathogenic, their impact on host biology can influence the distribution and transmission of vector-borne pathogens. The deer tick, Ixodes scapularis, is widely distributed in the Eastern United States and is an important transmitter of several human pathogens, including Borrelia species (Lyme disease) and Anaplasma phagocytophilum (anaplasmosis). Deer ticks also harbor a prevalent intracellular bacterium, Rickettsia buchneri, that is unique among Rickettsia species in several ways: 1) it is vertically inherited with high efficiency in the deer tick, but does not cycle between ticks and vertebrates in nature; 2) it is, astonishingly, the only Rickettsia species that has ever been detected in I. scapularis; and 3) its genome is substantially enriched with pseudogenes and MGEs that carry intriguing cargo, including genes for biotin synthesis, antibiotic synthesis and resistance, and nonribosomal peptide synthesis. Given its maintenance in deer ticks, and its arsenal of potential functions, R. buchneri stands to exert significant influence on the biology of this important disease vector. The long-term goal of this research is to determine the nature of the relationship between R. buchneri and I. scapularis. The current work is designed to advance this research goal by addressing significant challenges; namely, the lack of a high-quality reference genome, inconsistencies in infection rate and distribution data, and a dearth of information regarding strain-level genomic variation. The central hypothesis of this project is that high-resolution data on infection rate and genomic population substructure will elucidate R. buchneri's trajectory toward an obligate endosymbiotic lifestyle. The proposed work will gauge the extent of species-specific innovation in R. buchneri by using 1) long-read sequencing to generate a closed genome, 2) RNA-seq to confirm pseudogene prediction, and 3) phylogenomics to characterize genes and other genomic elements unique to R. buchneri (AIM 1). The current proposal work will also characterize the R. buchneri pan-genome by using 1) quantitative PCR to assess its infection rate among natural populations of deer ticks, 2) short-read deep sequencing to determine the distribution of R. buchneri genetic variants, alleles, and MGEs, and 3) phylogenomics to characterize the extent (and origin) of lateral gene transfers into R. buchneri (AIM 2). Illuminating R. buchneri genomic variation and tick infection frequency will lead to insights into its relationship with the deer tick and ultimately inform future efforts to use its repertoire of MGEs as gene drive tools for spreading factors to combat tick-borne diseases.

项目概要节肢动物疾病媒介的微生物居民对其宿主的生物学产生深远的影响，积极的（例如，营养获取、防御病原体）和消极的（例如，生殖寄生）。这支持这些微生物过程的机制是遗传变异和进化结果的结果通常由移动遗传元件（MGE）介导。即使这些常驻微生物尚不清楚致病性，它们对宿主生物学的影响可以影响媒介传播病原体的分布和传播。鹿蜱（Ixodes scapularis）广泛分布于美国东部，是蜱虫的重要传播者。几种人类病原体，包括伯氏疏螺旋体（莱姆病）和嗜吞噬细胞无形体（无形体病）。鹿蜱还含有一种普遍存在的细胞内细菌——布氏立克次体（Rickettsia buchneri），它是鹿蜱中独一无二的。立克次体种类有以下几种：1）它在鹿蜱中垂直遗传，效率很高，但不循环自然界中蜱虫和脊椎动物之间； 2）令人惊讶的是，它是唯一被发现的立克次体物种 I. 肩胛肌； 3) 它的基因组大量富含携带有趣货物的假基因和 MGE，包括生物素合成、抗生素合成和耐药性以及非核糖体肽合成的基因。给定 R. buchneri 在鹿蜱中的维持及其潜在功能库将发挥重大影响关于这种重要疾病媒介的生物学。这项研究的长期目标是确定 R. buchneri 和 I 之间关系的性质。肩胛肌。目前的工作旨在通过解决重大挑战来推进这一研究目标；即，缺乏高质量的参考基因组，感染率和分布数据不一致，缺乏有关菌株水平基因组变异的信息。该项目的中心假设是高分辨率有关感染率和基因组群体亚结构的数据将阐明 R. buchneri 走向必然的轨迹内共生生活方式。拟议的工作将通过以下方式衡量 R. buchneri 物种特异性创新的程度：使用 1) 长读长测序生成封闭基因组，2) RNA-seq 确认假基因预测，以及 3) 系统基因组学来表征 R. buchneri 特有的基因和其他基因组元件 (AIM 1)。目前的提案工作还将通过使用 1) 定量 PCR 评估 R. buchneri 的感染来表征 R. buchneri 泛基因组鹿蜱自然种群中的比率，2）短读长深度测序以确定 R 的分布。 buchneri 遗传变异、等位基因和 MGE，以及 3) 系统发育组学来表征侧向遗传的程度（和起源）基因转移至 R. buchneri (AIM 2)。阐明 R. buchneri 基因组变异和蜱感染频率将深入了解其与鹿蜱的关系，并最终为未来利用其 MGE 库的努力提供信息作为传播因子的基因驱动工具，以对抗蜱传疾病。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Orientia tsutsugamushi: analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium.

恙虫病东方体（Orientia tsutsugamushi）：对高度片段化和重复基因组的移动组的分析揭示了专性细胞内细菌中正在进行的横向基因转移。

DOI：
发表时间：
2023-05-11
期刊：
影响因子：
0
作者：
Giengkam, Suparat;Kullapanich, Chitrasak;Wongsantichon, Jantana;Adcox, Haley E;Gillespie, Joseph J;Salje, Jeanne
通讯作者：
Salje, Jeanne

Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium.

恙虫病东方体（Orientia tsutsugamushi）：对高度片段化和重复基因组的移动体的综合分析揭示了专性细胞内细菌持续横向基因转移的能力。

DOI：
发表时间：
2023-12-20
期刊：
影响因子：
4.8
作者：
Giengkam, Suparat;Kullapanich, Chitrasak;Wongsantichon, Jantana;Adcox, Haley E;Gillespie, Joseph J;Salje, Jeanne
通讯作者：
Salje, Jeanne