The Virulence-Associated Protein A (VapA) of Rhodococcus equi as a central manipulator of infected macrophages

马红球菌毒力相关蛋白 A (VapA) 作为受感染巨噬细胞的中央操纵者

• 批准号: 420695171
• 负责人: Professor Dr. Albert Haas
• 金额: --
• 依托单位: Institut für Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/420695171?language=en
• 关键词: Virulence; Associated; Protein; VapA; Rhodococcus

Rhodococcus equi is an important intracellular macrophage-localized pathogen in immunosuppressed humans and in foals. Using a mouse-based model, we have shown that VapA, as a central virulence factor of R. equi, changes intracellular transport in macrophages and increases the permeability of phagosome and lysosome membranes for protons. VapA action leads to the accumultation of lipid vesicles within the pathogen-containing phagosome. Here we plan to study the contribution of VapA-induced vesicle formation into the R. equi-containing vacuole (‘microautophagy’) to R. equi nutrition and pathogenesis. We will further study the regulation of vapA by environmental factors. Altogether these studies will contribute to understand how a single virulence factor (VapA) can govern all virulence events identified to date and how VapA helps supply the pathogen with nutrients. This knowledge will benefit not only research into bacterial pathogenicity in general but will also help design proper therapeutic targets and measures.

马红球菌是一种重要的细胞内巨噬细胞定位的病原体在免疫抑制的人和马驹。利用小鼠模型，我们已经表明，VapA，作为一个中心的毒力因子的R。Equi改变巨噬细胞的细胞内转运，并增加吞噬体和溶酶体膜对质子的渗透性。VapA作用导致脂质囊泡在含病原体的吞噬体内积累。在这里，我们计划研究VapA诱导的囊泡形成对R。含equit-containing液泡（“微自噬”）对R.马的营养和发病机制。我们将进一步研究环境因素对vapA的调节作用。总之，这些研究将有助于了解一个单一的毒力因子（VapA）如何控制迄今为止确定的所有毒力事件，以及VapA如何帮助为病原体提供营养。这一知识不仅有利于细菌致病性的研究，而且有助于设计适当的治疗靶点和措施。