Molecular determinants of sialic acid transport in pathogenic and commensal bacteria

病原菌和共生菌唾液酸转运的分子决定因素

• 批准号: 433072777
• 负责人: Dr. Gregor Hagelueken
• 金额: --
• 依托单位: Institut für Strukturbiologie
• 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/433072777?language=en
• 关键词: Molecular; determinants; sialic; acid; transport

Sialic acids are amino sugar acids that are found in large numbers in human tissue. There, they play an important role in a variety of biological processes, such as communication between cells, cell adhesion and -recognition. However, sialic acids are also an important source of energy and carbon for probiotic or commensal bacteria such as Bacteroides fragilis or Akkermansia muciniphila. At the same time, sialic acid in human tissue is also exploited by pathogens such as Haemophilus influenzae by incorporating the molecule into the lipopolysaccharides of their cell wall, making the bacteria harder to recognize by the human immune system. Both pathogenic and commensal bacteria use special transporters to take up sialic acid from human tissue. Commonly used are so-called TRAP (tripartite ATP-independent periplasmatic) transporters or MFS (major facilitator superfamily) transporters. The structural and functional investigation of these transporters is therefore of high interest. Therefore, the aim of this proposal is to investigate the mechanism of sialic acid TRAP and MFS transporters. Ideally, structures in different intermediate steps of the transport cycle will be determined by cryo-electron microscopy. At the same time, the transport process will be followed by single-molecule fluorescence microscopy through the use of special, conformation-selective probes. By combining these structural and functional data, deep insights into the function of bacterial sialic acid transporters shall be obtained.

唾液酸是在人体组织中大量发现的氨基酸。它们在细胞间通讯、细胞粘附和细胞识别等多种生物学过程中发挥着重要作用。然而，唾液酸也是益生菌或益生菌如脆弱拟杆菌或嗜粘蛋白阿克曼氏菌的重要能量和碳源。与此同时，人体组织中的唾液酸也被流感嗜血杆菌等病原体利用，通过将该分子掺入其细胞壁的脂多糖中，使细菌更难被人体免疫系统识别。致病菌和共生菌都使用特殊的转运蛋白从人体组织中吸收唾液酸。通常使用的是所谓的TRAP（三重ATP-独立的周质）转运蛋白或MFS（主要易化超家族）转运蛋白。因此，这些转运蛋白的结构和功能研究引起了人们的高度兴趣。因此，本研究的目的是探讨唾液酸TRAP和MFS转运蛋白的作用机制。理想情况下，运输周期的不同中间步骤中的结构将通过冷冻电子显微镜来确定。同时，运输过程将通过使用特殊的构象选择性探针进行单分子荧光显微镜检查。通过结合这些结构和功能数据，深入了解细菌唾液酸转运蛋白的功能。