Using genotype-to-phenotype analyses to identify the genetic determinants of gastroenteritis caused by the food-borne pathogen Campylobacter jejuni.

利用基因型到表型分析来确定食源性病原体空肠弯曲菌引起的胃肠炎的遗传决定因素。

• 批准号: 2433251
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2433251
• 关键词: Using; genotype; phenotype; analyses; identify

Campylobacter jejuni is the major causative agent of foodborne gastroenteritis across Europe. Contaminated chicken meat is the main source of infections and hence control of this pathogen is critical to food security in the poultry industry.The three major virulence determinants of C. jejuni are capsule, lipooligosaccharide and flagella. These structures are important for survival and colonisation of Campylobacter. Consequently, evasion of the immune system is paramount as these structures possess potential immunodominant epitopes that would otherwise result in early recognition of C. jejuni and its subsequent clearance.One mechanism of immune evasion is the decoration of protein structures with a variety of sugar molecules (glycans). A conserved epitope recognised by TLR-5 on the flagellin protein has been lost in C. jejuni. Loss of this epitope renders other bacteria, such as Salmonella, non-motile. However, the structural instability introduced into the flagella through mutations in the TLR-5 epitope has been compensated for by glycosylation of outer domains of the flagellin subunits (Kreutzberger et al., 2020). This highlights the degree to which glycans can play in the survival and immune evasion of Campylobacter. Further, these glycans are highly variable between strains due to differences in gene content, allelic variation and phase variation. Phase variation is a reversible mechanism that leads to ON/OFF switching of gene expression for contingency loci associated with homopolymeric tracts. This leads to different phenotypes through varied expression of genes, whether they are ON/OFF, and what combination is expressed. In our lab, it was shown that a delayed antibody response was observed in birds challenged with glycosylated FlaA when compared to recombinant FlaA protein. Therefore, our research aims to further investigate the contribution of genetic elements that introduce phenotypic variation towards Campylobacteriosis and the survival of Campylobacter.

空肠弯曲菌是欧洲食源性胃肠炎的主要病原体。受污染的鸡肉是感染的主要来源，因此控制该病原体对家禽业的食品安全至关重要。空肠有荚膜、脂寡糖和鞭毛。这些结构对于弯曲杆菌的存活和定殖是重要的。因此，逃避免疫系统是至关重要的，因为这些结构具有潜在的免疫显性表位，否则会导致C的早期识别。免疫逃避的一种机制是用各种糖分子（聚糖）装饰蛋白质结构。鞭毛蛋白上TLR-5识别的保守表位在C.空肠。该表位的丢失使得其他细菌，如沙门氏菌，不能运动。然而，通过TLR-5表位中的突变引入鞭毛的结构不稳定性已经通过鞭毛蛋白亚基的外部结构域的糖基化得到补偿（Kreutzberger et al.，2020年）。这突出了聚糖在弯曲杆菌的存活和免疫逃避中的作用程度。此外，由于基因含量、等位基因变异和相位变异的差异，这些聚糖在菌株之间高度可变。相位变化是一种可逆的机制，导致与均聚物束相关的应急基因座的基因表达的开/关切换。这导致不同的表型通过不同的基因表达，无论他们是开/关，什么组合表达。在我们的实验室中，结果表明，与重组FlaA蛋白相比，在用糖基化FlaA攻击的鸟类中观察到延迟的抗体应答。因此，我们的研究旨在进一步研究遗传因素对弯曲菌病和弯曲菌存活的影响。