[论文解读] Rapid host switching in generalist Campylobacter strains erodes the signal for tracing human infections

Bethany L. Dearlove, Alison J. Cody+4 more|arXiv (Cornell University)|Apr 7, 2015

Salmonella and Campylobacter epidemiology参考文献 11被引用 11

一句话总结

本研究揭示，与人类胃肠炎相关的广泛宿主适应性空肠弯曲杆菌（Campylobacter jejuni）和结肠弯曲杆菌（C. coli）菌株（克隆复合体ST-21、ST-45和ST-828）在家禽、牛和猪之间发生快速宿主转换，导致宿主关联的遗传信号被抹去。全基因组测序显示，89%的人类感染源自鸡，但宿主间高频率的传播掩盖了感染源的溯源，对基因组监测在疫情追踪中的可靠性构成挑战。

ABSTRACT

Campylobacter jejuni and Campylobacter coli are the biggest causes of bacterial gastroenteritis in the developed world, with human infections typically arising from zoonotic transmission associated with infected meat, especially poultry. Because this organism is not thought to survive well outside of the gut, host associated populations are genetically isolated to varying degrees. Therefore the likely origin of most Campylobacter strains can be determined by host-associated variation in the genome. This is instructive for characterizing the source of human infection at the population level. However, some common strains appear to have broad host ranges, hindering source attribution. Whole genome sequencing has the potential to reveal fine-scale genetic structure associated with host specificity within each of these strains. We found that rates of zoonotic transmission among animal host species in ST-21, ST-45 and ST-828 clonal complexes were so high that the signal of host association is all but obliterated. We attributed 89% of clinical cases to a chicken source, 10% to cattle and 1% to pig. Our results reveal that common strains of C. jejuni and C. coli infectious to humans are adapted to a generalist lifestyle, permitting rapid transmission between different hosts. Furthermore, they show that the weak signal of host association within these complexes presents a challenge for pinpointing the source of clinical infections, underlining the view that whole genome sequencing, powerful though it is, cannot substitute for intensive sampling of suspected transmission reservoirs.

研究动机与目标

• 调查与人类胃肠炎相关的常见空肠弯曲杆菌和结肠弯曲杆菌菌株中宿主转换的范围。
• 评估这些菌株中宿主相关的遗传特征是否能可靠地追溯人类感染的来源。
• 评估当宿主转换频繁时，全基因组测序在溯源中的局限性。

提出的方法

• 对来自人类及多种动物宿主（家禽、牛、猪）的弯曲杆菌分离株进行全基因组测序。
• 对克隆复合体ST-21、ST-45和ST-828进行系统发育分析，以评估不同宿主间菌株的遗传相关性。
• 通过群体遗传模型估算不同宿主物种之间的动物源性传播速率。
• 比较宿主相关的基因组变异，以确定每个克隆复合体中宿主信号的强度。
• 基于基因组相似性和传播动态，对人类临床病例进行统计溯源，确定其动物宿主来源。

实验结果

研究问题

• RQ1 常见弯曲杆菌菌株在家禽、牛和猪之间宿主转换的程度如何？
• RQ2 快速宿主转换如何影响临床分离株中宿主特异性遗传特征的可检测性？
• RQ3 对于宿主范围广泛的菌株，全基因组测序能否可靠地追溯人类弯曲杆菌感染的来源？
• RQ4 在宿主转换频率较高的情况下，人类感染中可归因于每种动物宿主的比例是多少？

主要发现

• 基于基因组相似性和传播模式，89%的人类弯曲杆菌感染归因于鸡源，10%归因于牛源，1%归因于猪源。
• ST-21、ST-45和ST-828克隆复合体中，动物宿主之间的动物源性传播速度极快，已基本抹去宿主相关的遗传信号。
• 广泛宿主适应性菌株中宿主转换的高频率削弱了仅依赖全基因组测序进行宿主溯源的可靠性。
• 由于频繁的跨物种传播，仅基于单一宿主物种的基因组数据无法准确追溯感染来源。
• 本研究证明，对所有疑似宿主进行密集采样是提高溯源准确性的关键。