Global control of Campylobacter jejuni biology by protein lysine acetylation

通过蛋白质赖氨酸乙酰化对空肠弯曲杆菌生物学进行全局控制

• 批准号: BB/R003491/1
• 负责人: Dave Kelly
• 金额: $ 56.67万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR003491%2F1
• 关键词: Global; control; Campylobacter; jejuni; biology

Some bacteria get into the food that we eat and cause food-poisoning. Some of these bacteria are quite common but are usually killed during cooking. When chicken meat is not cooked properly, one of these types of bacteria, called Campylobacter jejuni, is a particular problem. It normally lives harmlessly in the intestines of chickens but in humans causes severe diarrohea, which although not usually life-threatening, causes considerable impacts on time off work and in some cases can lead to serious complications. By understanding in detail the way in which this bacterium interacts with both its chicken and human hosts, we may be able to stop colonisation, prevent infection or design better treatments. C. jejuni has a small genome with only about 1650 genes and only a small number of proteins that are known to regulate gene expression. We hypothesise that in this bacterium, the control of the activity of proteins directly, through reversible modifications to their structure by additions of chemical groups, may assume greater importance than in bacteria with large genomes. In this project we wish to investigate one such modification; the addition of acetyl-groups (CH3-CO-) to proteins. We have discovered that over 70% of all of the proteins in C. jejuni are acetylated and that some of these modifications are reversible and controlled by a specific enzyme, a deacetylase. Moreover, we have found that important colonisation determinants such as the ability to swim and assimilate nitrogen for growth are impacted by acetylation. The project will investigate the consequences of acetylation at specific sites in selected proteins in detail and reveal how acetylation is controlled. The results should allow us to get a better knowledge of the way in which the bacterium uses acetylation in the colonisation process and to identify ways of disrupting acetylation, which could be exploited in future to limit its growth in chickens and to treat human infections.

一些细菌进入我们吃的食物中，导致食物中毒。其中一些细菌很常见，但通常会在烹饪过程中被杀死。当鸡肉没有被正确煮熟时，其中一种被称为空肠弯曲杆菌的细菌就会成为一个特别的问题。它通常生活在鸡的肠道中，对人无害，但会引起严重的腹泻，虽然通常不会危及生命，但会对下班时间造成相当大的影响，在某些情况下可能会导致严重的并发症。通过详细了解这种细菌与鸡和人类宿主的相互作用方式，我们可能能够阻止定植，防止感染或设计更好的治疗方法。空肠弯曲菌有一个很小的基因组，只有大约1650个基因和少量已知的调节基因表达的蛋白质。我们假设，在这种细菌中，通过添加化学基团对蛋白质结构进行可逆修改来直接控制蛋白质的活性，可能比在拥有大基因组的细菌中具有更重要的作用。在这个项目中，我们希望研究一种这样的修饰：在蛋白质中添加乙酰基(CH3-CO-)。我们已经发现，空肠弯曲菌中超过70%的蛋白质是乙酰化的，其中一些修饰是可逆的，并受一种特定的酶--脱乙酰酶控制。此外，我们还发现，重要的定植决定因素，如游泳和吸收生长所需的氮的能力，都受到乙酰化的影响。该项目将详细研究选定蛋白质中特定位置的乙酰化的后果，并揭示乙酰化是如何控制的。这些结果应该能让我们更好地了解细菌在定殖过程中使用乙酰化的方式，并确定破坏乙酰化的方法，未来可以利用这些方法来限制其在鸡中的生长和治疗人类感染。

项目成果

Bacterial periplasmic nitrate and trimethylamine-N-oxide respiration coupled to menaquinol-cytochrome c reductase (Qcr): Implications for electrogenic reduction of alternative electron acceptors.

• DOI: 10.1038/s41598-018-33857-2
• 发表时间: 2018-10-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Garg N;Taylor AJ;Kelly DJ
• 通讯作者: Kelly DJ