Mapping resistance to Campylobacter in the chicken

绘制鸡对弯曲杆菌的耐药性

• 批准号: BB/J006815/1
• 负责人: Mark Stevens
• 金额: $ 59.89万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ006815%2F1
• 关键词: Mapping; resistance; Campylobacter; chicken

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.

食品安全是英国政府日益重视的问题，食品安全是其中的一个关键组成部分。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321，000例，超过15，000例住院治疗和76例死亡。弯曲杆菌占英格兰和威尔士食源性疾病费用的三分之一，2008年估计为5.83亿英镑。它主要存在于家禽中，控制该水库中的生物体预计将降低人类感染的风险。“弯曲杆菌是一种高度复杂的有机体，我们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，才能更全面地了解它，并克服它构成的威胁。解决弯曲杆菌的挑战涉及两个BBSRC的三个战略重点粮食安全和基础生物科学支撑健康，除了利用系统的方法和新的研究工具。英国弯曲杆菌研究和创新战略，2010-2015年，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农场动物宿主中的细菌水平和食物链中交叉污染的可能性来降低人类弯曲杆菌感染的发生率。两个主要的研究重点是了解鸡的定殖和鸡的免疫反应，以及鸡对弯曲杆菌定殖的更大抵抗力。然而，这两个领域的研究都没有包括在最近的一项关于控制弯曲杆菌的联合呼吁中。对弯曲杆菌定殖具有显著先天抗性的鸡的可用性将是一种安全、具有成本效益的解决方案。我们已经证明，遗传变异会影响鸡对弯曲杆菌定殖的抵抗力，一个品系能够将肠道中的细菌水平降低10，000倍。对这些近交系鸡的复杂遗传分析表明，与抗性相关的一些区域或位点覆盖了已知的细菌抗性基因。在本提案中，我们将进一步研究这些位点，以定位有益基因或突变。我们将开展进一步的工作，以绘制抗性基因，并使用最新的方法，允许在整个基因组中选择基因。使用新一代高密度板等工具来检测单核苷酸多态性（同一位点两个不同个体之间DNA单个碱基的变化）（一次可以分析约750 k），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大大降低弯曲杆菌定殖水平的后代鸡。根据该战略的建议，我们将与业界（Aviagen，一家总部设在英国的公司，生产纯种鸡，全世界每年500亿只鸡中有50%以上来自纯种鸡）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方案中实施。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特定性状和候选动物的鉴定。虽然也存在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来控制农场弯曲杆菌的潜力，但我们认为，拟议的项目将允许有针对性地快速培育对弯曲杆菌定殖更具抗性的家禽品系。

项目成果

The genomic architecture of resistance to Campylobacter jejuni intestinal colonisation in chickens.

• DOI: 10.1186/s12864-016-2612-7
• 发表时间: 2016-04-18
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Psifidi A;Fife M;Howell J;Matika O;van Diemen PM;Kuo R;Smith J;Hocking PM;Salmon N;Jones MA;Hume DA;Banos G;Stevens MP;Kaiser P
• 通讯作者: Kaiser P

Colonization of a commercial broiler line by Campylobacter is under limited genetic control and does not significantly impair performance or intestinal health.

• DOI: 10.3382/ps/pey295
• 发表时间: 2018-12-01
• 期刊: Poultry science
• 影响因子: 4.4
• 作者: Bailey RA;Kranis A;Psifidi A;Watson KA;Rothwell L;Hocking PM;Kaiser P;Stevens MP;Avendano S
• 通讯作者: Avendano S

Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter.

• DOI: 10.1038/s41598-020-79005-7
• 发表时间: 2021-01-12
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Psifidi A;Kranis A;Rothwell LM;Bremner A;Russell K;Robledo D;Bush SJ;Fife M;Hocking PM;Banos G;Hume DA;Kaufman J;Bailey RA;Avendano S;Watson KA;Kaiser P;Stevens MP
• 通讯作者: Stevens MP

Combination of novel and public RNA-seq datasets to generate an mRNA expression atlas for the domestic chicken.

• DOI: 10.1186/s12864-018-4972-7
• 发表时间: 2018-08-07
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Bush SJ;Freem L;MacCallum AJ;O'Dell J;Wu C;Afrasiabi C;Psifidi A;Stevens MP;Smith J;Summers KM;Hume DA
• 通讯作者: Hume DA

Genetic control of Campylobacter colonisation in broiler chickens: genomic and transcriptomic characterisation

肉鸡中弯曲杆菌定植的遗传控制：基因组和转录组特征

• DOI: 10.1101/2020.04.14.040832
• 发表时间: 2020
• 作者: Psifidi A