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.

一些细菌进入我们吃的食物并引起食物毒品。其中一些细菌很常见，但通常在烹饪过程中被杀死。当鸡肉不正确煮熟时，这些类型的细菌之一（称为弯曲杆菌空肠）是一个特别的问题。它通常在鸡的肠道中无害地生存，但在人类中会导致严重的腹泻，尽管通常不会威胁生命，但会导致时间下班的大量影响，在某些情况下会导致严重的并发症。通过详细了解该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殖，防止感染或设计更好的治疗方法。我们发现了一种先前未见的方式，在这种方式中，这种细菌停止自身被通常由宿主产生的分子杀死，称为抗菌肽。这些分子试图将自己插入细菌的膜中，以形成孔，细菌含量泄漏出来，从而导致死亡。但是，空肠梭菌可以感觉到这些肽的存在，并且以响应的形式在其表面部署蛋白质可以结合它们并阻止它们进入细胞膜，从而使细菌对其作用高度抗性。在这项研究中，我们希望了解细菌对这些肽的感觉和反应，结合蛋白的起作用以及该系统控制的其他蛋白质的作用的细节。结果应该使我们能够更好地了解细菌在殖民过程中使用这种新型防御系统的方式并确定脆弱性，以后可能会利用这些脆弱性来限制其在鸡中的生长和治疗人类感染。