Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
Cell Mol Life Sci. 2018 Apr;75(7):1163-1178. doi: 10.1007/s00018-017-2696-5. Epub 2017 Oct 27.
Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme-substrate and -inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.
许多致病性细菌需要通过鞭毛介导的运动来在其宿主中定植和持续存在。幽门螺杆菌和空肠弯曲菌是与多种人类病理相关的鞭毛ε变形菌，包括胃炎、急性腹泻、胃癌和神经紊乱。在这两个物种中，鞭毛蛋白的糖基化与一种不寻常的糖假氨基（Pse）在功能性鞭毛的生物合成中起着至关重要的作用，从而影响细菌的运动性和致病性。Pse 仅存在于致病性细菌中。其通过六个连续的酶促步骤的生物合成在幽门螺杆菌和空肠弯曲菌中得到了广泛研究。这篇综述强调了鞭毛糖基化的重要性，并详细介绍了通过对酶-底物和酶-抑制剂复合物的生化、晶体学和诱变研究获得的 Pse 途径中酶的结构见解。预计，了解 Pse 合成酶的催化机制的基础结构和分子基础将为开发新型抗菌药物铺平道路。
