The mechanism and role of erythrocyte invasion by Francisella tularensis

图拉氏方济氏菌是最具传染性的生物体之一，因吸入一种 细菌可能导致一种称为图拉热症的致命疾病。因此，它被归类为 被疾病控制和预防中心列为A类生物防御剂。许多 种子研究表明，图拉氏杆菌在巨噬细胞内复制的能力是 与这种生物的致病机制有关的。在接下来的几年里，我的实验室帮助 通过阐明与非链球菌属的相互作用，推动方济各菌研究领域的发展 巨噬细胞在感染期间也是极其重要的，因为这些细胞提供了一个避难所 防止免疫，允许细菌增殖，并提供对抗生素的保护。虽然 图拉氏丝虫领域的许多工作都集中在巨噬细胞内的生物学上。 在生物体中，与其他类型细胞的相互作用尚未得到彻底的研究。也许是因为 我们实验室最令人惊讶的发现是，图拉氏丝虫入侵并持续存在 在红细胞中。这种入侵增强了图拉氏杆菌在扁虱体内生存的能力。 (重要的疾病媒介)在一顿血餐之后。在此应用程序中，我们将检验假设 红血球的入侵是硬体长期定植所必需的 传染给哺乳动物。 我们之前已经证明，红细胞表面蛋白，带3是必需的 侵袭和与这种表面蛋白相互作用可能是操纵 Ankyrin-1介导的血影蛋白细胞骨架。此外，我们还证明了图拉里尼斯氏杆菌 通过VI型分泌系统(T6SS)将PdpC分泌到红细胞中，该效应器是 是入侵所必需的。另一种T6SS效应物Opia会在红细胞中产生和积聚 在细菌滞留期间。在本应用程序中，我们将探索上述主机和 细菌蛋白深入了解红细胞入侵和持久性的机制 在这些宿主细胞中。

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.