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

• 批准号: 10115952
• 负责人: Timothy P Driscoll
• 金额: $ 24.38万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 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/10115952
• 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; Deer Tick; 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

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.

项目总结