Francisella tularensis invasion of human erythrocytes

土拉弗朗西斯菌入侵人红细胞

• 批准号: 8492011
• 负责人: JOSEPH A HORZEMPA
• 金额: $ 10.62万
• 依托单位: WEST LIBERTY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492011
• 关键词: Antibiotic Therapy; Applications Grants; Arthropod Vectors; Arthropods; Attenuated; Attenuated Vaccines; Bacteria; Biological; Biology; Blood; Breathing; Categories; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Complement Receptor; Data; Disease; Environment; Erythrocytes; Evaluation; Francisella; Francisella tularensis; Future; Goals; Human; Immune; Immune system; In Vitro; Infection; Infectious Agent; Integration Host Factors; Intracellular Space; Invaded; Investigation; Knowledge; Lead; Life; Literature; Mediating; Microbe; Molecular; Organism; Pathogenesis; Pathway interactions; Patients; Phagocytes; Pilum; Process; Reporting; Research; Role; Seminal; Specimen; Staging; System; Therapeutic; Ticks; Tularemia; Virulence; Work; biodefense; cell type; disease transmission; disorder prevention; in vitro Assay; in vivo; innovation; macrophage; mutant; novel; pathogen; pathogenic bacteria; research study; transmission process; vaccine development

DESCRIPTION (provided by applicant): Francisella tularensis is one of the most infectious organisms as inhalation of a single bacterium can lead to a fatal disease referred to as tularemia. It has therefore been categorized by the Centers for Disease Control and Prevention as a Category A biodefense agent. Many seminal studies have shown that the ability of F. tularensis to replicate within macrophages is a feature of this organism during infection. Only recently we have appreciated that interactions with non-macrophages are also extremely important during infection as these cells provide a niche for immune protection, proliferation, and other unexplored roles. Although much of the work in the field of F. tularensis has focused on the intra-macrophage biology of this organism, interactions with other cell types have not been thoroughly investigated. Using both in vivo and in vitro approaches, we present strong evidence that F. tularensis invades and persists in erythrocytes. The proposed work will provide an understanding of a previously uncharacterized phenomenon by a Category A biodefense agent - namely erythrocyte invasion by F. tularensis. The two aims to investigate erythrocyte invasion by F. tularensis are: 1) To examine the molecular mechanism of F. tularensis erythrocyte invasion. 2) To determine the role of erythrocyte invasion by F. tularensis. As erythrocyte invasion of F. tularensis has not yet been described in the literature, the studies proposed here will open up a new line of research. We will investigate a potential role in pathogenesis, arthropod transmission, and disease persistence. Our work will involve evaluation of fixed blood from tularemia patients to assess the degree of erythrocyte invasion during human infection. We will also examine the mechanism by which F. tularensis erythrocyte invasion occurs, exposing novel host-microbe molecular pathways. In addition to enhancing our understanding of an important Category A biodefense agent, the research proposed may also uncover general systems implemented by diverse intracellular pathogens. The bacterial pathogen Francisella tularensis is a signficant bioterror threat. The research descibed in this proposal will make important advances toward understanding how this organism invades red blood cells. The results of this work may lead to vaccine development and potential therapeutics that alter the Francisella- erythrocytre interactions.

描述(申请人提供)：图拉氏方济氏菌是最具传染性的生物之一，因为吸入单一细菌可导致一种称为图拉热症的致命疾病。因此，它被疾病控制和预防中心归类为A类生物防御剂。许多开创性的研究表明，图拉氏丝虫在巨噬细胞内复制的能力是这种生物在感染过程中的一个特征。直到最近，我们才意识到与非巨噬细胞的相互作用在感染过程中也非常重要，因为这些细胞为免疫保护、增殖和其他未知角色提供了一个利基环境。尽管图拉氏丝虫领域的许多工作都集中在这种生物的巨噬细胞内生物学上，但与其他类型细胞的相互作用还没有得到彻底的研究。使用体内和体外方法，我们提出了图拉氏丝虫侵入并持续存在于红细胞中的有力证据。这项拟议的工作将提供对A类生物防御剂以前未描述的现象的理解--即图拉氏丝虫对红细胞的入侵。这两项研究的目的是研究图拉氏丝虫对红细胞的入侵： 1)探讨图拉氏狸殖吸虫红细胞侵袭的分子机制。 2)确定图拉氏原虫对红细胞的侵袭作用。 由于尚未有文献报道图拉氏丝虫对红细胞的侵袭，本文提出的研究将开辟一条新的研究路线。我们将研究其在发病机制、节肢动物传播和疾病持久性方面的潜在作用。我们的工作将包括评估图拉热症患者的固定血液，以评估在人类感染期间红细胞入侵的程度。我们还将研究图拉氏丝虫红细胞入侵的机制，揭示新的宿主-微生物分子途径。除了加强我们对一种重要的A类生物防御剂的理解外，拟议的研究还可能揭示由不同的细胞内病原体实施的一般系统。 图拉氏方济各氏菌是一种重大的生物恐怖威胁。这项提案中描述的研究将在了解这种生物如何入侵红细胞方面取得重要进展。这项工作的结果可能导致疫苗的开发和改变方济各氏菌与红细胞相互作用的潜在疗法。