Global control of enzyme activity in the food-borne human pathogen Campylobacter jejuni

空肠弯曲杆菌是最常见的细菌性食源性病原体，估计每年造成800，000例病例仅在英国就有100多例胃肠炎，主要来自未煮熟的鸡肉。BBSRC从食物链中根除这种病原体的优先战略要求更好地了解其生物学，以确定新的干预目标。其代谢的一个重要方面，以前没有研究的是通过翻译后修饰（PTM）的蛋白质活性的控制。最近已经变得明显的是，在特定赖氨酸残基上的可逆乙酰化是细菌中用于控制多种酶的活性的普遍机制。我们在C.空肠中编码候选赖氨酸脱乙酰酶（Sirtuin同源物）的氨基酸序列。我们还发现，一种关键的代谢酶，乙酰辅酶A合成酶，有一个保守的赖氨酸残基，在其他细菌中已知是乙酰化的。因此，本项目将利用分子生物学和蛋白质组学技术，寻求揭示乙酰化在酶活性全球控制中的重要性。

Campylobacter jejuni is the commonest bacterial food-borne pathogen, responsible for an estimated 800,000 cases p.a. of gastroenteritis in the UK alone, mainly from undercooked chicken. The BBSRC priority strategy for eradicating this pathogen from the food chain demands greater understanding of its biology to identify new intervention targets. One important aspect of its metabolism that has not been investigated previously is the control of protein activity by post-translational modifications (PTMs). Recently it has become apparent that reversible acetylation on specific lysine residues is a widespread mechanism in bacteria for control of the activity of diverse enzymes. We have identified a conserved gene in C. jejuni that encodes a candidate lysine deacetylase (a Sirtuin homologue). We have also found that a key metabolic enzyme, acetyl-CoA synthetase, has a conserved lysine residue that in other bacteria is known to be acetylated. This project will therefore seek to uncover the importance of acetylation in the global control of enzyme activity using molecular biological and proteomic techniques.