A novel bacterial defence system against antimicrobial peptides: Implications for host colonisation in the food-borne pathogen Campylobacter jejuni

一种针对抗菌肽的新型细菌防御系统：对食源性病原体空肠弯曲菌宿主定植的影响

• 批准号: BB/K005510/1
• 负责人: Dave Kelly
• 金额: $ 44.57万
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK005510%2F1
• 关键词: novel; bacterial; defence; system; against

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. We have discovered a previously unsuspected way in which this bacterium stops itself being killed by molecules normally produced by the host, called antimicrobial peptides. These molecules try to insert themselves into the membrane of the bacteria to create a pore, through which the bacterial contents leak out, causing death. But C. jejuni can sense the presence of these peptides, and in response deploys a protein at its surface which we have shown can bind them and stop them getting to the cell membrane, which therefore makes the bacteria highly resistant to their action. In this research, we wish to understand the details of how the bacteria sense and respond to these peptides, how the binding protein works and the role of some other proteins that are controlled by this system. The results should allow us to get a better knowledge of the way in which the bacterium uses this novel defence system in the colonisation process and to identify vulnerabilities, which could be exploited in future to limit its growth in chickens and to treat human infections.

有些细菌进入我们吃的食物，引起食物中毒。其中一些细菌很常见，但通常在烹饪过程中被杀死。当鸡肉没有正确烹饪时，其中一种称为空肠弯曲杆菌的细菌是一个特别的问题。它通常无害地生活在鸡的肠道中，但在人类中会引起严重的腹泻，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，在某些情况下会导致严重的并发症。通过详细了解这种细菌与其鸡和人类宿主相互作用的方式，我们可能能够阻止定植，预防感染或设计更好的治疗方法。我们已经发现了一种以前没有想到的方式，这种细菌可以阻止自己被宿主通常产生的分子杀死，称为抗菌肽。这些分子试图将自己插入细菌的细胞膜中，形成一个小孔，细菌的内容物通过这个小孔泄漏出来，导致死亡。但鉴证空肠可以感觉到这些肽的存在，并在其表面部署一种蛋白质作为响应，我们已经证明这种蛋白质可以结合它们并阻止它们进入细胞膜，因此使细菌对它们的作用具有高度抗性。在这项研究中，我们希望了解细菌如何感知和响应这些肽的细节，结合蛋白如何工作以及由该系统控制的其他一些蛋白质的作用。这些结果应该使我们能够更好地了解这种细菌在殖民过程中使用这种新型防御系统的方式，并确定未来可以利用的弱点，以限制其在鸡中的生长和治疗人类感染。