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仍然是新发传染病研究中的知识空白。蜱传疾病继续困扰着人类健康，并且考虑到媒介的高繁殖潜力、在极端条件下生存的能力以及传播寄生、病毒和细菌病原体的能力，了解蜱媒介内病原体的定植尤其相关。公共卫生。其中一种病原体是蜱传回归热（RF）螺旋体。 RF螺旋体的全球分布和对人类健康的经济负担未被充分认识，特别是考虑到该疾病的流行及其对贫困国家人口的影响，但我们不了解病原体如何在蜱虫媒介中适应。该媒介的一个独特特征是蜱虫的寿命极长，两次进食之间可以持续数年，但细菌仍然存活并具有传染性。此外，螺旋体的进食速度和随后的传播与其他蜱传疾病显着不同，这进一步强调了了解 RF 螺旋体如何在蜱体内生存的必要性。阻碍疾病预防疗法发展的一个限制是对蜱载体 RF 螺旋体定植的分子事件了解甚少。为了解决这个问题，我们建立了一个体内系统来研究 RF 螺旋体的一种疏螺旋体 (Borrelia turicatae) 的完整蜱-哺乳动物感染周期。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这些基因，并且计算机分析表明这些基因编码推定的外膜蛋白 (Omps)。我们在大肠杆菌中扩增、克隆并表达了 15 个基因，并建议针对重组蛋白生成兔血清，从而使我们能够确定这些蛋白是否暴露在表面。着眼于已确认的 Omp，我们将确定蜱虫必须定殖的两个区域（中肠和唾液腺）内 Omp 的差异产生，以确保螺旋体继续生命周期。完成本提案后，我们将更好地了解蜱虫感染期间 B. turicatae 的表面蛋白质组，并将确定蜱虫媒介的中肠和唾液腺中 Omp 的产生是否存在差异。我们的研究结果将为 R01 竞争性应用提供必要的数据，以调查中肠和唾液腺中独特产生的 Omp 是否是 B. turicatae 在这些组织中定植所必需的。

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