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

有些细菌进入我们吃的食物，导致食物中毒。其中一些细菌很常见，但通常在烹饪过程中被杀死。当鸡肉没有煮熟时，其中一种被称为空肠弯曲杆菌的细菌就会产生特别的问题。它通常在鸡的肠道中无害，但在人类中会引起严重的腹泻，尽管通常不会危及生命，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。我们发现了一种以前没有想到的方法，这种细菌可以阻止自己被通常由宿主产生的分子杀死，这种分子被称为抗菌肽。这些分子试图将自己插入细菌的膜中，形成一个孔，细菌内容物通过这个孔泄漏出去，导致死亡。但是空肠梭菌可以感知到这些肽的存在，作为回应，在其表面部署了一种蛋白质，我们已经展示了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有很强的抵抗力。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受该系统控制的其他一些蛋白质的作用。这一结果应该能让我们更好地了解这种细菌在定植过程中使用这种新型防御系统的方式，并确定其脆弱性，这可能在未来被利用来限制其在鸡体内的生长和治疗人类感染。

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.