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）：了解不同自然环境内的微生物适应性仍然是新兴传染病研究中知识的差距。 tick传播的疾病继续困扰人类健康，鉴于向量高生殖潜力，在极端条件下生存的能力以及传播寄生虫，维尔和细菌病原体的能力，因此了解tick载体内病原体定殖的能力与公共卫生特别相关。这样一种病原体是tick传播的复发发烧（RF）螺旋体。 RF螺旋体对人类健康的全球分配和经济负担不足，尤其是考虑到贫困国家中该疾病对人口的流行和影响，但我们不了解病原体在壁虱载体中的适应方式。矢量的一个独特特征是，tick虫的寿命非常长，并且可以在喂养之间数年，但是细菌仍然可行且可传播。此外，喂食和随后的螺旋体传播的速度与其他tick传播疾病明显不同，进一步强调了需要了解RF螺旋体如何在壁虱中生存。阻止疾病发展疗法的一种局限性是对造成tick载体RF螺旋体定植的分子事件的不良理解。为了解决这个问题，我们已经建立了一个体内系统，以研究RF螺旋体的Borrelia turicatae的完整tick哺乳动物感染周期。我们已经确定了一系列连续的质粒局部基因，该基因在tick感染过程中对螺旋体进行了调节，并且在计算机分析中表明，这些基因编码了推定的外膜蛋白（OMP）。我们已经放大，克隆并表达了大肠杆菌中的15个基因，并提议针对重组蛋白产生兔子血清，从而使我们能够确定蛋白质是否表面暴露。为了关注确认的OMP，我们将确定在the虫必须定居的两个区域内OMP的差异产生，以确保螺旋体持续生命周期，中肠和唾液腺。该提案完成后，我们将更好地了解tick感染期间曲霉芽孢杆菌的表面蛋白质组，我们将确定在tick载体的中肠和唾液腺内是否会差异化OMP。我们的发现将生成竞争性R01应用所需的数据，该数据是否在中肠和唾液腺内产生的唯一作用对于这些组织的曲霉定植是必需的。

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