Genomic features of host adaptation of Campylobacter in low-income settings

摘要 有强有力的流行病学证据表明，人类适应了人畜共患病原体弯曲杆菌。然而，在这方面， 这种适应的基因组特征尚未得到系统的评价。本报告的总体目标 该项目的目的是确定弯曲杆菌的特定基因组特征，这些特征与适应环境有关。 人类宿主的长期目标是将这些知识应用于全球参考数据库， 归因和指导改进疾病控制措施，以减少全球弯曲杆菌负担 人类的疾病。我们的中心假设是，在高度流行的环境中，长期接触使得 适应人类宿主，而不是我们通常观察到的短暂感染流行病学， 弯曲杆菌以前的证据表明，人类适应了以前提出的长期携带， 免疫抑制患者和某些与人类疾病相关的弯曲杆菌谱系， 慢性后遗症，如GBS，在人类宿主之外很少发现。我们已经确定了这些 在秘鲁亚马逊地区进行的两项纵向队列研究中， 儿童年监测，20,000粪便样本和850弯曲杆菌分离。具体而言，我们证明a） 持续性弯曲杆菌感染和携带超过70%的儿童完成0至24个月的随访， B）C.与全球临床收集相比，来自人类的空肠菌株多样性 c）仅在人类宿主中描述的菌株（例如ST-403、ST 2802和ST-2803）的高比例， 2993），与全球参考集合相比，以及d）人类的基因组大小显著减小 衍生C.空肠基因组与全球参考数据库进行比较。为了验证我们的假设，我们将 1)确定人类持续性弯曲杆菌感染的基因组特征，以及2）确定 时空聚集性感染代表人传人。该项目将联合 一群在流行病学、进化论和生物学方面具有专业知识的有成就的研究人员， 生物学、弯曲杆菌基因组学和生物信息学，为战略性和针对性疾病控制提供信息 在人类MDR记录率最高的地区之一进行弯曲杆菌控制干预 弯曲杆菌感染。[The该项目是创新的方式，它应用微生物GWAS方法，以资本化 在从明确的纵向队列研究中获得的特殊菌株库上， 适应。] [High这项研究产生的人类宿主适应性的质量证据将是范例 转向用于控制弯曲杆菌的策略，可能会改变临床管理， 弯曲杆菌肠炎。]

ABSTRACT There is strong epidemiologic evidence of human adaption of the zoonotic pathogen Campylobacter. However, the genomic features of such adaptation have not been systematically evaluated. The overall objective of this project is to identify specific genomic features of Campylobacter that are associated with adaptation to the human host with the long-term goal of applying this knowledge to global reference databases to inform host attribution and guide improved disease control measures to reduce the global burden of Campylobacter disease in humans. Our central hypothesis is that in highly endemic settings, long-term exposure has allowed adaptation to the human host, as opposed to the transient infection epidemiology we usually observe with Campylobacter. Previous evidence of human adaption has been previously suggested by prolonged carriage in immunosuppressed patients and that certain Campylobacter lineages associated with human disease and chronic sequelae such as GBS, are rarely found outside the human host. We have identified these observations in two longitudinal cohort studies in the Peruvian Amazon that cumulatively comprise over 1400 child-years of surveillance, 20,000 stool samples and 850 Campylobacter isolates. Specifically, we evidence a) persistent Campylobacter infection and carriage in over 70% of children with complete 0 to 24-month follow-up, b) high-level of C. jejuni strain diversity derived from humans compared to the global collection of clinical genomes, c) high proportion of strains described exclusively in human hosts (such ST-403, ST2802 and ST- 2993), as compared to the global reference collection and d) considerable reduced genome size of human derived C. jejuni genomes compared to the global reference collection. In order to test our hypothesis, we will 1) Identify genomic features of persistent Campylobacter infections in humans, and 2) Determine if spatiotemporally clustered infections represent human to human transmission. The proposed project will unite a highly complementary group of accomplished researchers with expertise in epidemiology, evolutionary biology, Campylobacter genomics, and bioinformatics to inform strategic and targeted disease control interventions for Campylobacter control in an area with one of the highest documented rates of human MDR Campylobacter infection. [The project is innovative in the way it applies microbial GWAS methods to capitalize on an exceptional strain bank derived from well-defined longitudinal cohort studies to efficiently identify host adaptation.] [High quality evidence of human host adaptation generated by this study would be paradigm shifting to strategies used to control Campylobacter and would likely to alter the clinical management of Campylobacter enteritis.]