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Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in vitro and in vivo models

机译:食源性空肠弯曲菌弯曲杆菌在体内和体外的全基因组适应性分析

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摘要

Campylobacter is the most common cause of foodborne bacterial illness worldwide. Faecal contamination of meat, especially chicken, during processing represents a key route of transmission to humans. There is a lack of insight into the mechanisms driving C. jejuni growth and survival within hosts and the environment. Here, we report a detailed analysis of C. jejuni fitness across models reflecting stages in its life cycle. Transposon (Tn) gene-inactivation libraries were generated in three C. jejuni strains and the impact on fitness during chicken colonisation, survival in houseflies and under nutrient-rich and –poor conditions at 4 °C and infection of human gut epithelial cells was assessed by Tn-insertion site sequencing (Tn-seq). A total of 331 homologous gene clusters were essential for fitness during in vitro growth in three C. jejuni strains, revealing that a large part of its genome is dedicated to growth. We report novel C. jejuni factors essential throughout its life cycle. Importantly, we identified genes that fulfil important roles across multiple conditions. Our comprehensive screens showed which flagella elements are essential for growth and which are vital to the interaction with host organisms. Future efforts should focus on how to exploit this knowledge to effectively control infections caused by C. jejuni.
机译:弯曲杆菌是全世界食源性细菌性疾病的最常见原因。加工过程中粪便对肉类(尤其是鸡肉)的污染是向人类传播的关键途径。缺乏对空肠弯曲杆菌在宿主和环境中生长和存活的机制的了解。在这里,我们报告了反映模型生命周期各个阶段的空肠弯曲杆菌适应性的详细分析。在三种空肠弯曲杆菌菌株中产生了转座子(Tn)基因失活文库,并评估了其在鸡定居过程中的适应性,家蝇以及在4°C下在营养丰富和不良的条件下的存活率以及人类肠道上皮细胞感染的影响通过Tn插入位点测序(Tn-seq)。共有331个同源基因簇对于三种空肠弯曲杆菌菌株的体外生长适应性至关重要,这表明其基因组的很大一部分致力于生长。我们报告了整个生命周期中必不可少的新型空肠弯曲菌因子。重要的是,我们鉴定了在多种条件下均起重要作用的基因。我们全面的筛选显示哪些鞭毛元素对于生长必不可少,哪些对于与宿主生物的相互作用至关重要。未来的工作应集中在如何利用这些知识来有效控制空肠弯曲杆菌引起的感染上。

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