Mapping resistance to Campylobacter in the chicken

食品安全日益成为英国政府的优先事项，食品安全是其中的关键组成部分。弯曲杆菌是英国最常见的食物中毒原因，2008年在英格兰和威尔士估计有32.1万起病例，其中1.5万多人住院，76人死亡。弯曲杆菌占英格兰和威尔士食源性疾病成本的三分之一，2008年估计为5.83亿英镑。它主要在家禽中发现，在该水库控制该生物有望降低人类感染的发生率。“弯曲杆菌是一种高度复杂的生物，只有通过在微生物学、免疫学和分子生物学领域开展世界级的研究，我们才能更全面地了解它，并克服它所构成的威胁……除了开发系统方法和新的研究工具外，应对弯曲杆菌挑战还涉及BBSRC三大战略重点中的两个，即粮食安全和支撑健康的基础生物科学。”道格拉斯·凯尔教授，BBSRC首席执行官。英国弯曲杆菌研究与创新战略（2010-2015）由FSA、BBSRC、DEFRA、DARDNI和苏格兰政府联合资助。资助者的首要目标是通过降低弯曲杆菌在其农场动物宿主中的水平和食物链中交叉污染的可能性来减少人类感染弯曲杆菌的发生率。两个主要的研究重点是了解鸡的定植和鸡的免疫反应，以及开发对弯曲杆菌在鸡体内定植的更大抵抗力。然而，这两个领域的研究都没有包括在最近的弯曲杆菌控制研究的联合呼吁中。可获得对弯曲杆菌定植具有显著先天抗性的鸡将是一种安全、经济的解决方案。我们已经证明，遗传变异影响了鸡对弯曲杆菌定植的抵抗力，其中一个品系相对于另一个品系能够将肠道中弯曲杆菌的水平降低1万倍。对这些自交系的复杂遗传分析表明，一些与抗性相关的区域或位点位于已知的细菌抗性基因之上。在本研究中，我们将进一步研究这些基因座，以定位有益基因或突变。我们将进一步开展抗性基因图谱的工作，并使用最新的方法，在整个基因组中选择基因。利用诸如新一代高密度面板等工具来检测单核苷酸多态性（两个不同个体在同一位点的单个DNA碱基变化）（一次可分析约750k），我们可以识别具有候选抗性基因的动物，这些基因可用于选择具有强大抗性和弯曲杆菌定植水平大大降低的后代鸡。根据该战略的建议，我们将与产业界（Aviagen公司是一家总部位于英国的纯种鸡公司，全世界每年生产的500亿只鸡中有50%以上是纯种鸡）合作开展这项基因研究，因为基因关联研究必须在家禽育种计划中实施。对弯曲杆菌的抗性可能取决于多个基因，抗性品系的选择将取决于对特定性状和候选动物的鉴定。虽然通过改善卫生和生物安全、饮食调整、新型抗菌剂和疫苗接种也有可能在农场控制弯曲杆菌，但我们相信，拟议的项目将允许有针对性和快速的方法来培育对弯曲杆菌定植更具抗性的家禽品种。

Food security is an increasing priority for the UK Government and food safety is a key component of this. Campylobacter is the most common cause of food poisoning in the UK and is responsible for an estimated 321,000 estimated cases in England and Wales in 2008, with over 15,000 hospitalisations and 76 deaths. Campylobacter accounts for a third of the cost of food-borne illness in England and Wales, estimated at £583 million in 2008. It is found mainly in poultry and control of the organism in this reservoir is expected to lower the inclidence of human infection."Campylobacter is a highly complex organism and we will only be able to understand it more fully and to overcome the threat it poses by deploying world-class research across microbiology, immunology and molecular biology... Addressing the Campylobacter challenge involves two of the three BBSRC strategic priorities of food security and basic bioscience underpinning health, in addition to exploiting systems approaches and new research tools." Professor Douglas Kell, BBSRC CEO.The UK Research and Innovation Strategy for Campylobacter, 2010-2015, is joint funded by the FSA, BBSRC, DEFRA, DARDNI and the Scottish Government. The overarching aim for the funders is to reduce the incidence of Campylobacter infections in humans, through reduction of the level of the bacterium in its farm animal hosts and the potential for cross-contamination in the food chain. Two of the main research priorities are understanding colonisation in the chicken and the chicken's immune response, and development of greater resistance to Campylobacter colonisation in the chicken. However, research in either of these areas was not included in a recent joint call for research into control of Campylobacter.The availability of chickens with significant innate resistance to Campylobacter colonisation would represent a safe, cost-effective solution. We have shown that genetic variation influences resistance to Campylobacter colonisation in chickens, with one line able to reduce levels of the bacterium in the gut by up 10,000-fold relative to another line. Complex genetic analysis in these inbred chicken lines has indicated that some of the regions, or loci, associated with resistance overlie known bacterial resistance genes. In this proposal we will investigate these loci further to locate the beneficial genes or mutations.We will carry out further work to map resistance genes, coupled with using the latest methods that allow selection of genes throughout the whole genome. Using tools such as new generations of high density panels to detect single nucleotide polymorphisms (changes in a single base of DNA between two different individuals at the same site) (~750k can be analysed at once), we can identify animals with candidate resistance genes that can be used to select future generations of chickens with robust resistance and greatly reduced levels of Campylobacter colonisation. As recommended by the Strategy, we will carry out this genetic research in collaboration with industry (Aviagen, a UK-based company that produces the pedigree chickens from which are generated over 50% of the world's 50 billion chickens every year), since gene association studies must be implemented in poultry breeding programmes. It is likely that resistance to Campylobacter depends on multiple genes and the selection of resistant lines will depend on the identification of specific traits and candidate animals. Though potential also exists to control Campylobacter on farm via improvements to hygiene and biosecurity, dietary modification, novel antimicrobial agents and vaccination, we believe that the proposed project would allow a targeted and rapid approach to breeding lines of poultry more resistant to Campylobacter colonisation.