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The mechanism and role of erythrocyte invasion by Francisella tularensis

土拉弗朗西斯菌侵袭红细胞的机制及作用

基本信息

批准号：
10730228
负责人：
JOSEPH A HORZEMPA
金额：
$ 42.15万
依托单位：
WEST LIBERTY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10730228
关键词：
ANK1 gene Animals Antibiotics Arbovirus Infections Arthropod Vectors Arthropods Bacteria Bacterial Proteins Binding Binding Proteins Biochemistry Biological Biology Bite Blood Categories Cell Surface Proteins Cells Centers for Disease Control and Prevention (U.S.)Complex Cytoskeleton Dangerousness Data Dermacentor Disease Disease Vectors Epithelial Cells Erythrocyte Anion Exchange Protein 1 Erythrocyte Membrane Erythrocytes Fibroblasts Francisella Francisella tularensis Funding Hepatocyte Immune system Immunity In Vitro Infection Infectious Agent Inhalation Invaded Investigation Knowledge Laboratories Life Link Macrophage Mammals Manuscripts Mediating Membrane Proteins Molecular Molecular Genetics Mus Organism Pathogenesis Phagocytes Planet Earth Principal Investigator Proliferating Protein Secretion Proteins Publications Research Role Seminal Site Spectrin System Testing Ticks Tularemia Virulent Work Zoonoses alveolar epithelium biodefense cell type combat extracellular host-microbe interactions insight neutrophil novel pathogen pathogenic bacteria programs sucking tick feeding transmission process

项目摘要

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 associated with the pathogenesis of this organism. In subsequent years, my laboratory helped to move the field of Francisella research forward by illuminating that interactions with non- macrophages are also extremely important during infection as these cells provide a sanctuary from immunity, allow for bacterial proliferation, and provide protection from antibiotics. 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. Perhaps the most surprising finding of our laboratory was the discovery that F. tularensis invades and persists in erythrocytes. This invasion enhances the ability of F. tularensis bacteria to survive in ticks (important disease vectors) following a blood meal. In this application, we will test the hypothesis that erythrocyte invasion is required for long-term colonization of ticks and subsequent transmission to mammals. We have previously shown that the erythrocyte surface protein, Band 3 is required for invasion and that interaction with this surface protein may be required for manipulation of the spectrin cytoskeleton through Ankyrin-1. Moreover, we have shown that F. tulareniss bacteria secrete PdpC into erythroyctes via the type VI secretion system (T6SS), and that this effector is required for invasion. OpiA, another T6SS effector, is produced and accumulates in erythrocytes during bacterial persistence. In this application, we will explore these aforementioned host and bacterial proteins to gain insight into the mechanism of erythrocyte invasion and the persistence within these host cells.

土拉菌是最具传染性的单一吸入微生物之一