Virulence and immunity in Rhodococcus equi

马红球菌的毒力和免疫力

• 批准号: 183796-2006
• 负责人: Prescott, John
• 金额: $ 4.43万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=364159
• 关键词: Virulence; immunity; Rhodococcus; equi

Rhodococcus equi is an important cause of a serious bacterial pneumonia in foals that can live inside the main phagocytic cell in their lungs.  It is really surprising that such a hostile environment allows this bacterium to survive, but it has some genes on a unique genetic structure, a "pathogenicity island", that allow it to do so. Our interest in this bacterial infection is not only that it causes economic loss and demoralization on horse-breeding farms around the world but also that it is related to Mycobacterium tuberculosis, the agent of human tuberculosis that infects over one-third of the human population.  This makes this organism of great comparative medical interest, since we may be able to use it to model aspects of tuberculosis in humans, for example testing novel antibacterial treatments. The work we are doing is designed to understand at a very detailed molecular level exactly how this bacterium is able to interfere with normal killing by phagocytic cells, especially what signals tells the bacterium that it is inside a phagocyte and how it then switches on proteins that it needs to survive in this usually hostile environment and switches off the proteins that it no longer needs. We are particularly interested in the role of iron and magnesium in controlling these switches, as well as in how the "pathogenicity island" interacts or "talks" to the genome, and vice versa. We will use many advanced techniques to study this, including inactivation of different genes. We will test many inactivated genes to see if they reduce the ability of this bacterium now to cause disease, and will find out whether we can use one or more of these mutants to immunize young foals by mouth, so that we can safely stop this awful disease.

马红球菌是马驹严重细菌性肺炎的重要原因，它可以生活在马驹肺部的主要吞噬细胞内。  令人惊讶的是，如此恶劣的环境允许这种细菌生存，但它在独特的基因结构（“致病岛”）上有一些基因，使其能够生存。我们对这种细菌感染的兴趣不仅在于它给世界各地的养马场带来经济损失和士气低落，而且还在于它与结核分枝杆菌有关，结核分枝杆菌是人类结核病的病原体，感染了超过三分之一的人口。  这使得这种生物体具有巨大的比较医学意义，因为我们可以用它来模拟人类结核病的各个方面，例如测试新型抗菌治疗。我们正在做的工作旨在在非常详细的分子水平上准确了解这种细菌如何能够干扰吞噬细胞的正常杀伤，特别是哪些信号告诉细菌它位于吞噬细胞内部，以及它如何打开它在这种通常充满敌意的环境中生存所需的蛋白质，并关闭它不再需要的蛋白质。我们特别感兴趣的是铁和镁在控制这些开关中的作用，以及“致病岛”如何与基因组相互作用或“对话”，反之亦然。我们将使用许多先进技术来研究这一点，包括不同基因的失活。我们将测试许多失活的基因，看看它们是否会降低这种细菌现在引起疾病的能力，并将找出我们是否可以使用这些突变体中的一种或多种通过口腔对幼马进行免疫，以便我们可以安全地阻止这种可怕的疾病。