Role of AKT1 & SIVA1 in resistance to avian salmonellosis

AKT1 的作用

• 批准号: BB/J015296/1
• 负责人: Mark Stevens
• 金额: $ 47.33万
• 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: 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%2FJ015296%2F1
• 关键词: Role; AKT1; SIVA1; resistance; avian

Poultry are a key reservoir of human Salmonella infections owing to the ability of some strains to colonise the avian intestines and reproductive tract. Birds often carry the bacteria in the absence of overt symptoms; however some types of Salmonella cause severe typhoid-like diseases in poultry that exert substantial welfare and economic costs. Global population growth and rising affluence are fuelling demand for poultry meat and eggs, and a need exists to enhance the supply and safety of such. Though vaccines are used in layers in some countries, most of the 55 billion chickens reared annually worldwide lack protection against Salmonella infection. We and others have discovered that some chickens exhibit heritable differences in resistance to Salmonella. It may be feasible to selectively breed for birds with improved resilience to Salmonella infection; however this requires the identification of resistance-associated factors and knowledge of how they act. By analysing the genetic material of birds that differ in resistance, we have located a region of the chicken chromosome that confers protection against typhoidal salmonellosis, both in laboratory studies and commercial poultry populations. Recent studies have now resolved the region associated with resistance to just a handful of genes. It is highly plausible that variation affecting two genes in this region (AKT1 and SIVA1) explains why birds react to Salmonella in different ways, as the encoded proteins control host processes that impact on the fate of bacteria. For example, AKT1 and SIVA1 control the death of infected cells and the induction of immune responses, but have opposing activities. It is not possible for us to predict how the genetic changes affecting these genes will alter their expression or activity. Moreover, it is unclear how such factors may control the growth and spread of Salmonella in birds. We therefore propose to:1. Examine if birds normally respond to Salmonella infection by activating the expression or function of AKT1 and SIVA1. We will examine this in cells cultured from chickens, as well as in intact birds, and associate any differences with host responses and the fate of the bacteria.2. Examine if lines of chicken known to differ in resistance to Salmonella infection vary in the levels or activation of AKT1 and SIVA1. 3. Use specific inhibitors and bacterial strains to establish that AKT1 activation is necessary for Salmonella to grow and spread in birds.4. Define the nature, frequency and consequences of genetic changes affecting AKT1 and SIVA1 in commercial poultry populations. This will aid the selective breeding of chickens that show improved resilience to Salmonella infection.We are fortunate to have the support of one of the world's largest poultry breeding companies (Erich Wesjohann Group), who will provide birds, genome sequences, expertise and 10% of total project costs. This reflects the value of the proposed studies to the industry. The consortium has productively collaborated and the proposed studies are a timely, logical and feasible extension of our recent joint research.

家禽是人类沙门氏菌感染的主要宿主，因为某些菌株能够在禽类肠道和生殖道定植。鸟类通常在没有明显症状的情况下携带这种细菌;然而，某些类型的沙门氏菌会在家禽中引起严重的伤寒样疾病，造成巨大的福利和经济损失。全球人口增长和日益富裕正在刺激对禽肉和禽蛋的需求，因此需要加强此类产品的供应和安全。虽然疫苗在一些国家用于蛋鸡，但全世界每年饲养的550亿只鸡中的大多数缺乏对沙门氏菌感染的保护。我们和其他人已经发现，一些鸡在对沙门氏菌的抵抗力方面表现出遗传差异。选择性地繁殖对沙门氏菌感染具有更好的抵抗力的鸟类可能是可行的;然而，这需要鉴定与抗性相关的因素并了解它们如何起作用。通过分析抗性不同的鸟类的遗传物质，我们已经定位了鸡染色体的一个区域，该区域在实验室研究和商业家禽种群中都能保护鸡免受伤寒沙门氏菌病的侵害。最近的研究现在已经解决了与少数基因的抗性相关的区域。影响该区域两个基因（AKT 1和SIVA 1）的变异解释了为什么鸟类以不同的方式对沙门氏菌做出反应，因为编码的蛋白质控制着影响细菌命运的宿主过程。例如，AKT 1和SIVA 1控制感染细胞的死亡和免疫应答的诱导，但具有相反的活性。我们无法预测影响这些基因的遗传变化将如何改变它们的表达或活性。此外，目前还不清楚这些因素如何控制沙门氏菌在鸟类中的生长和传播。因此，我们建议：检查鸟类是否通过激活AKT 1和SIVA 1的表达或功能对沙门氏菌感染作出正常反应。我们将在从鸡培养的细胞中检查这一点，以及在完整的鸟类中，并将任何差异与宿主反应和细菌的命运联系起来。检查已知对沙门氏菌感染具有不同抗性的鸡系是否在AKT 1和SIVA 1的水平或激活方面存在差异。3.使用特定的抑制剂和细菌菌株来确定AKT 1激活是沙门氏菌在鸟类中生长和传播所必需的。定义商业家禽种群中影响AKT 1和SIVA 1的遗传变化的性质、频率和后果。我们很幸运得到了世界上最大的家禽养殖公司之一（Erich Wesjohann Group）的支持，该公司将提供家禽、基因组序列、专业知识和10%的项目总成本。这反映了拟议研究对业界的价值。该联盟进行了富有成效的合作，拟议的研究是我们最近联合研究的及时、合理和可行的延伸。

项目成果

Salmonella pathogenesis and host-adaptation in farmed animals.

养殖动物的沙门氏菌发病机制和宿主适应。

• DOI: 10.1016/j.mib.2021.05.013
• 发表时间: 2021
• 期刊: Current opinion in microbiology
• 影响因子: 5.4
• 作者: Stevens MP

Salmonella in domestic animals

家畜中的沙门氏菌

• DOI: 10.1079/9781845939021.0104
• 发表时间: 2013
• 作者: Kaiser P