Newton001: Identification of host and pathogen glucose metabolism modulation during Mycobacterium leprae infection of human macrophages and Schwann ce

Newton001：麻风分枝杆菌感染人类巨噬细胞和雪旺细胞期间宿主和病原体葡萄糖代谢调节的鉴定

• 批准号: MR/M026434/1
• 负责人: Johnjoe McFadden
• 金额: $ 9.29万
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM026434%2F1
• 关键词: Newton001; Identification; host; pathogen; glucose

According to World Health Organization, the number of leprosy new cases in 2012 stood at 189,018 around the world. Although not fatal, leprosy is responsible for more than 12 thousands cases of irreversible motor disability and deformity per year in the world. The disease is caused by the Mycobacterium leprae, an obligatory intracellular pathogen that preferentially infects skin macrophages and Schwann cells causing nerve damage and scarring, which results in the disfigurement and the classic hand and foot deformities of leprosy. Brazil has 33,303 cases/year of leprosy, being the most affected country in Latin America, representing 14 percent of the global number of cases and is surpassed only by India, which has approximately 134,752 new cases per year. Intracellular bacteria must obtain nutrients from their host cell and grow by either adapting their own metabolic pathways or manipulating the metabolism of the host. Understanding how they obtain nutrients from their host and how they utilize them will lead to better understanding the infection and may inspire novel ways to grow the bacteria for vaccine or drug studies; which is particularly relevant to the leprosy bacillus which cannot be grown in pure culture in the laboratory.In this project we will use a newly-developed developed technique called 13C flux spectral analysis to investigate the metabolism of M. leprae in its host cell. The M. leprae cells will be grown in mouse footpads, and then incubated in media containing a mixture of 12C and 13C-labelled glucose and metabolites extracted for analysis. We will use another technique called mass spectrometry to determine the distribution of 12C and 13C carbon in these metabolites and computer analysis of the data will reveal clues to both the nutrients used by M. leprae and how it utilises them. The work will be published in a peer-reviewed journal and may lead to novel approaches to growing the leprosy bacillus and developing new drugs.

根据世界卫生组织的数据，2012年全球麻风新病例数为189，018例。麻风病虽然不是致命的，但每年在世界上造成12 000多例不可逆转的运动残疾和畸形。这种疾病是由麻风分枝杆菌引起的，麻风分枝杆菌是一种专性细胞内病原体，它优先感染皮肤巨噬细胞和许旺细胞，造成神经损伤和瘢痕，导致毁容和麻风病的典型手足畸形。巴西每年有33，303例麻风病，是拉丁美洲受影响最严重的国家，占全球病例数的14%，仅次于印度，印度每年约有134，752例新病例。胞内细菌必须从其宿主细胞获得营养，并通过适应自身代谢途径或操纵宿主代谢来生长。了解它们如何从宿主那里获得营养以及如何利用它们将有助于更好地了解感染，并可能激发新的方法来培养细菌用于疫苗或药物研究;这是特别相关的麻风杆菌，不能在纯培养在实验室中生长。在这个项目中，我们将使用一个新的-13 C通量谱分析技术研究了M.麻风病在它的宿主细胞。分枝麻风细胞将在小鼠脚垫中生长，然后在含有12 C和13 C标记的葡萄糖和提取用于分析的代谢物的混合物的培养基中孵育。我们将使用另一种称为质谱的技术来确定这些代谢物中12 C和13 C碳的分布，计算机分析数据将揭示M所使用的营养素的线索。以及如何利用它们。这项工作将发表在一份同行评议的杂志上，并可能导致新的方法来培养麻风杆菌和开发新的药物。