Relapsing Fever Spirochete Protein Production within the Vector

载体内回归热螺旋体蛋白的产生

• 批准号: 8908201
• 负责人: Job E Lopez
• 金额: $ 19.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-24 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8908201
• 关键词: Address; Africa; Arthropod Vectors; Arthropods; Bacteria; Bacterial Infections; Biological; Blood; Borrelia burgdorferi; Borrelia turicatae; Cessation of life; Characteristics; Child; Childhood; Chills; Complex; Computer Simulation; Country; Data; Development; Disease; Economic Burden; Emerging Communicable Diseases; Ensure; Environment; Epithelium; Escherichia coli; Event; Fever; Genes; Genetic; Goals; Grant; Health; Hour; Human; Immune; Immune Sera; Immunofluorescence Immunologic; In Vitro; Infection; Infectious Diseases Research; Knowledge; Laboratories; Laser Scanning Confocal Microscopy; Life; Life Cycle Stages; Lipoproteins; Longevity; Lyme Disease; Maintenance; Malaria; Mammals; Manuscripts; Membrane Proteins; Methods; Microbe; Midgut; Mind; Mining; Molecular; Mus; Nausea and Vomiting; Order Spirochaetales; Ornithodoros; Oryctolagus cuniculus; Peptide Signal Sequences; Phase; Plasmids; Population; Preparation; Prevalence; Production; Proteins; Proteome; Public Health; Recombinant Proteins; Recombinants; Recurrence; Relapsing Fever; Research; Resources; Risk; Rocky Mountain Spotted Fever; Saliva; Salivary Glands; Series; Serum; Surface; System; Testing; Therapeutic; Tick-Borne Diseases; Ticks; Time; Tissues; Tuberculosis; Up-Regulation; Vector-transmitted infectious disease; Work; World Health Organization; feeding; gene function; in vivo; microbial; pathogen; prevent; reproductive; tissue fixing; transmission process; vector

DESCRIPTION (provided by applicant): Understanding microbial adaption within different natural environments remains a gap in knowledge in emerging infectious disease research. Tick-borne diseases continue to afflict human health, and given the vectors high reproductive potential, the ability to survive in extreme conditions, and the ability to transmit parasitic, virl, and bacterial pathogens, understanding pathogen colonization within the tick vector is particularly relevant to public health. One such pathogen is tick-borne relapsing fever (RF) spirochetes. The global distribution and economic burden of RF spirochetes on human health is underappreciated, especially considering the prevalence and impact of the disease on populations in impoverished countries, yet we do not understand how the pathogen adapts within the tick vector. A unique characteristic of the vector is that the ticks are extremely long-lived and can go years between feedings, yet the bacteria remain viable and transmissible. Additionally, the rapidity of feeding and subsequent transmission of the spirochetes differs significantly from other tick-borne diseases, further emphasizing the need to understand how RF spirochetes survive within the tick. One limitation that has prevented the development of disease preventing therapeutics has been a poor understanding of the molecular events contributing to RF spirochete colonization of the tick vector. To address this, we have established an in vivo system to study the complete tick-mammalian infectious cycle for Borrelia turicatae, a species of RF spirochete. We have identified a series of 20 consecutive plasmid localized genes that the spirochetes up- regulate during tick infection, and an in silico analysis indicated that the genes encode for putative outer membrane proteins (Omps). We have amplified, cloned, and expressed 15 of the genes in E. coli and propose to generate rabbit serum against the recombinant proteins, allowing us to determine if the proteins are surface exposed. Focusing on the confirmed Omps, we will determine the differential production of the Omps within two regions of the tick that B. turicatae must colonize to ensure the spirochetes continued life cycle, the midgut and salivary glands. At the completion of this proposal, we will better understand the surface proteome of B. turicatae during tick infection and we will determine if Omps are differentially produced within the midgut and salivary glands of the tick vector. Our findings will generate the data necessary for a competitive R01 application investigating if the Omps uniquely produced within the midgut and salivary glands are necessary for B. turicatae colonization of these tissues.

描述（由申请人提供）：了解微生物在不同自然环境中的适应性仍然是新兴传染病研究中的一个知识空白。蜱虫传播的疾病继续困扰人类健康，鉴于蜱虫媒介具有高生殖潜力、在极端条件下生存的能力以及传播寄生虫、病毒和细菌病原体的能力，了解蜱虫媒介内的病原体定植尤其重要。与公共卫生相关。一种这样的病原体是蜱传回归热（RF）螺旋体。RF螺旋体对人类健康的全球分布和经济负担未得到充分重视，特别是考虑到该疾病对贫困国家人口的流行和影响，但我们不了解病原体如何适应蜱虫媒介。该载体的一个独特特征是，蜱虫寿命极长，可以在两次喂食之间存活数年，但细菌仍然具有活力和传播性。此外，螺旋体的进食速度和随后的传播速度与其他蜱传疾病显著不同，进一步强调了了解RF螺旋体如何在蜱内存活的必要性。阻止疾病预防治疗剂开发的一个限制是对促成RF螺旋体定殖于蜱虫载体的分子事件的理解不足。为了解决这个问题，我们建立了一个体内系统，研究完整的蜱哺乳动物感染周期的疏螺旋体，RF螺旋体的一个物种。我们已经鉴定了一系列20个连续的质粒定位基因，螺旋体在蜱感染期间上调，并且计算机分析表明这些基因编码推定的外膜蛋白（Omps）。我们扩增、克隆了其中15个基因，并在大肠杆菌中表达。大肠杆菌，并建议产生兔血清对重组蛋白，使我们能够确定，如果蛋白质的表面暴露。关注确认的Omp，我们将确定B的蜱的两个区域内Omp的差异产生。螺旋体必须定殖以确保螺旋体的持续生命周期、中肠和唾液腺。在完成这一建议后，我们将更好地了解B的表面蛋白质组。我们将确定Omp是否在蜱虫感染期间的中肠和唾液腺内差异产生。我们的研究结果将产生必要的数据，为竞争R01的应用调查，如果OMP独特的中肠和唾液腺内产生的是必要的B。这些组织的尿酸盐定殖。

项目成果

Tick-Borne Relapsing Fever Spirochetes in the Americas.

• DOI: 10.3390/vetsci3030016
• 发表时间: 2016-01-01
• 期刊: Veterinary sciences
• 影响因子: 2.4
• 作者: Lopez, Job E;Krishnavahjala, Aparna;Bermudez, Sergio
• 通讯作者: Bermudez, Sergio

Erratum: Lopez, J.E., et al. Tick-Borne Relapsing Fever Spirochetes in the Americas. Vet. Sci. 2016, 3, 16.

勘误表：Lopez, J.E. 等人。

• DOI: 10.3390/vetsci6040098
• 发表时间: 2019
• 期刊: Veterinary sciences
• 影响因子: 2.4
• 作者: Lopez,JobE;Krishnavajhala,Aparna;Garcia,MelissaN;Bermudez,Sergio
• 通讯作者: Bermudez,Sergio

Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated gene in the tick-mammalian transmission cycle of relapsing fever spirochetes.

• DOI: 10.1038/s41598-017-14959-9
• 发表时间: 2017-11-10
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Luo Z;Kelleher AJ;Darwiche R;Hudspeth EM;Shittu OK;Krishnavajhala A;Schneiter R;Lopez JE;Asojo OA
• 通讯作者: Asojo OA