A small RNA regulation of virulence in Lyme disease pathogen

莱姆病病原体毒力的小RNA调节

• 批准号: 10218725
• 负责人: Xiuli Yang
• 金额: $ 7.73万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218725
• 关键词: Address; Affect; Antibiotics; Arbovirus Infections; Area; Bacteria; Bacteria sigma factor KatF protein; Base Pairing; Binding; Binding Proteins; Biological; Biological Process; Biology; Body Temperature; Borrelia; Borrelia burgdorferi; Cells; Complex; Data; Development; Environment; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genetic Translation; Genome; Goals; Impairment; Infection; Intercistronic Region; Intergenic DNA; Ixodes; Kanamycin; Kanamycin A; Life Cycle Stages; Location; Lyme Disease; Mammals; Measures; Messenger RNA; Microbe; Microbial Physiology; Mus; Mutagenesis; Nature; Northern Blotting; Nucleotides; Open Reading Frames; Order Spirochaetales; Organism; Pathogenesis; Play; Preventive; Proteins; RNA; RNA Binding; RNA-Binding Proteins; Regulation; Regulator Genes; Regulon; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Role; Seminal; Series; Small RNA; Stimulus; Temperature; Therapeutic; Ticks; Tissues; Untranslated RNA; Untranslated Regions; Virulence; Work; base; differential expression; environmental change; enzootic; mRNA Stability; microbial; pathogen; pathogenic bacteria; response; tissue tropism; transmission process

Project Summary/Abstract Lyme disease, a prevalent arthropod-borne disease, is caused by the bacterial pathogen Borrelia burgdorferi. The microbes live in an intricate enzootic life cycle involving both Ixodes ticks and diverse mammalian species. To survive in its complex cycle and navigate through disparate sets of tissue environments, such as ones in mammalian hosts or in ticks, B. burgdorferi must regulate gene expression in a tight temporal and spatial manner, although the mechanism of such gene regulation remains unclear. Posttranscriptional gene regulation via a variety of small regulatory RNAs (sRNAs) is one mechanism of modulating gene expression in bacteria. Base pairing between the sRNAs and target mRNAs can trigger alterations in mRNA translation and stability, thereby influencing target gene expression. The small RNAs also bind to proteins, either sequestering or affecting the activities of proteins. Previous studies have reported that a small RNA, DsrABb, regulates RpoS gene expression in B. burgdorferi. Moreover, recent studies identified over 1000 B. burgdorferi sRNAs that are differentially regulated by environmental conditions, suggesting that sRNAs may play a role in gene regulation for spirochete adaptation during its enzootic cycle, although their precise functions or importance in spirochete biology and infectivity remain largely enigmatic. Most recently, an intergenic non-coding small RNA located upstream of bbd18, called ittA, was characterized and shown to be required for optimal infectivity and tissue tropism in B. burgdorferi. In fact, the intergenic region of bbd17 and bbd18 was reported to harbor a small RNA 0735 (SR0735), that is highly expressed at 37°C (mammalian host body temperature). Our preliminary data showed that the insertion of a kanamycin cassette upstream of SR0735 affects B. burgdorferi infectivity and decreases the level of SR0735, as shown in Northern blot and RT-PCR analyses, suggesting a critical importance of SR0735 in microbial virulence. The goals of our current proposal are to study the potential role of this sRNA in spirochete biology and virulence, and to identify its potential target RNA and/or protein binding partners. This study will uncover the sRNA regulatory mechanisms in spirochete biology and may help to decipher the functions of sRNAs in spirochete virulence and pathogenesis.

项目摘要/摘要 莱姆病是一种普遍的节肢动物传播疾病，是由细菌病原体Borrelia burgdorferi引起的。 微生物生活在复杂的enzootic生命周期中，涉及ixodes tick和潜水的哺乳动物物种。 在复杂的周期中生存并浏览不同组织环境的集合，例如 哺乳动物宿主或在壁虱中，B。Burgdorferi必须在紧密的临时和空间中调节基因表达 方式，尽管这种基因调节的机制尚不清楚。转录后基因 通过多种小调节RNA（SRNA）调节是调节基因表达的一种机制 细菌。 SRNA和靶mRNA之间的基础配对可以触发mRNA翻译的改变，并且 稳定性，从而影响靶基因表达。小RNA还与蛋白质结合，要么隔离 或影响蛋白质的活性。先前的研究报告说，一个小的RNA DSRABB调节RPO B. burgdorferi中的基因表达。此外，最近的研究确定了超过1000 B. burgdorferi srnas 受环境条件的差异调节，表明SRNA可能在基因调节中起作用 对于螺旋体的适应在其enzootic循环中，尽管它们在螺旋体中的精确功能或重要性 生物学和感染在很大程度上仍然是神秘的。最近，一个位于基因间的非编码小RNA BBD18的上游被称为ITTA，被表征并证明是最佳感染和组织所必需的 B. Burgdorferi中的Tropism。实际上，据报道，BBD17和BBD18的基因间区域有一个小的 RNA 0735（SR0735），在37°C（哺乳动物宿主体温）上高度表达。我们的初步 数据表明，SR0735上游的卡纳米霉素盒的插入会影响B. burgdorferi感染 并降低SR0735的水平，如北印迹和RT-PCR分析所示，这表明了关键 SR0735在微生物病毒中的重要性。我们目前的提议的目标是研究潜在角色 螺旋体生物学和病毒中的SRNA，并鉴定其潜在的靶标RNA和/或蛋白质结合 合作伙伴。这项研究将发现螺旋体生物学中的SRNA调节机制，可能有助于 解释了srNA在螺旋体病毒和发病机理中的功能。