Utilisation of iron from transferrin and lactoferrin by campylobacters

铁是细菌在细胞内许多基本过程中所需要的一种营养物质。作为对细菌感染的反应的一部分，动物限制可获得的铁量。在哺乳动物中，乳铁蛋白(在粘膜分泌物中)和转铁蛋白(在血清中)与游离铁紧密结合，从而限制其可获得性。不幸的是，成功的致病细菌已经找到了从宿主那里夺回铁的方法。细菌在宿主体内获取铁的机制通常由细菌细胞外表面的一个特定孔和相关的运输系统组成，该系统使铁在细胞内可用。感染人类的最重要的食物相关细菌是弯曲杆菌，因此在英国造成了许多痛苦和经济损失。弯曲杆菌通常生活在许多动物的肠道中，特别是鸡，在那里它们并不总是引起疾病。然而，当人类食用被弯曲杆菌污染的食物时，随之而来的可能是非常令人不快的痉挛腹泻。食品生产商努力将消费者的食物中毒风险降至最低，但如果能从农场动物的肠道中消除弯曲杆菌，特别是鸡的肠道中的弯曲杆菌，它将对人类健康产生重大影响，因为它每年可以防止数千例食源性疾病。如果要实现控制，重要的是我们要更好地了解弯曲杆菌是如何在肠道定植的。弯曲杆菌的几种成分对肠道的生长至关重要，它们参与了宿主体内铁的获取。在我们的初步工作中，我们已经在弯曲杆菌中发现了一个系统，它可以直接从乳铁蛋白和转铁蛋白中捕捉铁来支持细菌的生长。这项工作已经确定了细菌细胞外表面的特定孔洞以及将铁转移到细胞内部的相关运输系统的候选者。我们的项目目标是验证系统组件的识别，并确定从乳铁蛋白/转铁蛋白中去除铁以允许细菌生长的方法。随着对铁获取系统有了更好的了解，我们将能够确定它是否适合在农场进行干预，以阻止动物肠道的生长，减少食物污染。

Iron is a nutrient that bacteria need for many essential processes in the cell. As part of the response to infection by bacteria, animals restrict the amount of iron available. In mammals lactoferrin (in mucosal secretions) and transferrin (in serum) tightly bind free iron to restrict its availability. Unfortunately, successful disease-causing bacteria have found ways to grab iron back from the host. The bacterial mechanisms involved in acquiring iron in the host usually consist of a specific pore on the outer surface of the bacterial cell and an associated transport system that makes the iron available inside the cell. The most important food-associated bacterium that infects humans is Campylobacter and as such is responsible for much misery and economic loss in the UK. Campylobacters normally live in the intestine of many animals, notably chickens, where they do not always cause disease. However, when humans eat food contaminated with campylobacters, an highly unpleasant cramping diarrhoea can follow. Food producers strive to minimise the risks of food poisoning for consumers, but if Campylobacter could be eliminated from the intestines of farm animals, particularly chickens, it would have a significant impact on human health by preventing many thousands of cases of food borne disease each year. If control is to be achieved it is important that we better understand how Campylobacter colonises the intestine. Several components of campylobacters that are essential for growth in the intestine are involved in acquiring iron within the host. In our preliminary work, we have identified a system in campylobacters that can grab iron directly from lactoferrin and transferrin to support bacterial growth. This work has identified candidates for the specific pore on the outer surface of the bacterial cell and the associated transport system that moves the iron to the inside of the cell. Our project objectives are to verify the identify of the components of the system and determine the methods by which iron is removed from lactoferrin/transferrin to allow bacterial growth. With a better understanding of the iron acquisition system we will be able to determine if it would be an suitable target for intervention on the farm in order to block growth in the animal gut and reduce food contamination.