Modelling Campylobacter survival and spread through poultry processing: a population genomics approach.

弯曲杆菌是发达国家细菌性胃肠炎最常见的病因。这种微生物是鸟类和其他动物肠道微生物群的常见组成部分，人类感染通常与食用受污染的肉类或家禽有关。在调查人类感染的根源方面已经付出了相当大的努力，有大量证据表明，与鸡有关的菌株是疾病的主要来源。这并不是因为鸡的致病性更强而是因为鸡在农场受到了高水平的污染从加工到零售的整个过程中都是如此。弯曲杆菌是一种不适应在宿主外生存的生物，其传播和可能通过家禽加工增加的机制尚不清楚。在农场消灭弯曲杆菌可以解决这个问题，但这需要昂贵的生物安全干预措施，而且在现代家禽业的加工过程中，可能还有其他方面的干预措施是有效和可行的。在这个项目中，我们将使用最先进的方法，从家禽加工和人类疾病的关键阶段确定弯曲杆菌菌株的整个遗传密码（基因组）。这些遗传信息将用于研究生理性状（表现型）的变化，如在特定阶段/生态位的生存，是如何由基因的变化（基因型）决定的。种群遗传结构的变化将被用于建立一个数学模型，该模型可以模拟弯曲杆菌通过对某些基因的选择而通过的过程，例如有机体在鸡肠道外生存所需的那些基因。通过运行具有不同参数的模型模拟，我们将研究(i)菌株如何通过加工变化，（ii）负责疾病相关谱系存活和增殖的因素，以及（iii）加工中弯曲杆菌可以最有效地灭绝的点。这种了解弯曲杆菌生存和传播的系统方法将为有针对性的干预提供信息。

Campylobacter is the most common cause of bacterial gastro-enteritis in the developed world. This organism is a common constituent of the gut micro-biota of birds and other animals and human infection is usually associated with the consumption of contaminated meat or poultry. Considerable effort has gone into investigating the root to human infection and there is substantial evidence that strains associated with chicken are a major source of disease. This is not thought to be because chicken types are more pathogenic but because chickens have high levels of contamination on the farm and this is maintained all the way through processing to retail. The mechanisms by which Campylobacter, an organism that is poorly adapted to survival outside of the host, spreads and potentially increases through poultry processing are poorly understood. Eliminating Campylobacter on the farm could tackle the problem but it requires expensive biosecurity interventions and there may other points through processing where interventions could be effective and practicable in the modern poultry industry. In this project we will use state-of-the-art means of determining the entire genetic code (genome) of Campylobacter strains from key stages through poultry processing and human disease. This genetic information will be used to examine how variation in the physical traits (phenotype), such as survival in a particular stage/niche, are determined by changes to the genes (genotype). Changes in the genetic structure of the population will be used to inform a mathematical model that simulates the passage of Campylobacter through processing based upon selection for certain genes, for example those required by the organism to survive outside of the chicken gut. By running model simulations with different parameters we will investigate (i) how the strains change through processing, (ii) the factors responsible for the survival and proliferation of disease associated lineages, and (iii) points in processing where Campylobacter can be most effectively pushed to extinction. This systems approach to understanding Campylobacter survival and spread will inform targeted interventions.