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

低收入环境中弯曲杆菌宿主适应的基因组特征

基本信息

批准号：
10615827
负责人：
Margaret N Kosek
金额：
$ 17.95万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10615827
关键词：
Acceleration Acute Affect Animal Feed Animal Husbandry Antibiotics Area Bioinformatics Biology Birds Birth Campylobacter Campylobacter infection Campylobacter jejuni Child Chronic Clinical Clinical Management Cohort Studies Collaborations Collection Communicable Diseases Data Data Set Databases Diagnostic Disease Disease Outbreaks Domestic Fowls Enteral Epidemiologist Epidemiology Event Family Focal Infection Food Processing Gastroenteritis General Practitioners Genetic Genome Genomics Goals Guillain Barré Syndrome Household Human Hygiene Immunocompromised Host Individual Infection Intervention Investigation Investments Knowledge Localized Disease Longitudinal cohort study Low income Measures Metabolic Methods Microbe Mission Modeling Organism Outcome Pediatric cohort Peruvian Phenotype Population Positioning Attribute Productivity Public Health Research Research Personnel Risk Ruminants Salmonella enterica Sanitation Series Source Specialist Testing United States National Institutes of Health Vaccines Veterinarians Water Zoonoses antimicrobial chronic infection cohort design disorder control enteritis follow-up future outbreak genome analysis genome sequencing genome wide association study human disease human pathogen improved innovation microbial model organism pathogen prevent spatiotemporal stool sample transmission process whole genome

项目摘要

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.]

抽象的有强有力的流行病学证据表明人类对人畜共患病原体弯曲杆菌的适应。然而，这种适应的基因组特征尚未得到系统评估。本次活动的总体目标该项目的目的是确定与适应环境相关的弯曲杆菌的特定基因组特征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以告知宿主归因并指导改进疾病控制措施，以减少弯曲杆菌的全球负担人类疾病。我们的中心假设是，在高度流行的环境中，长期暴露使得对人类宿主的适应，而不是我们通常观察到的短暂感染流行病学弯曲杆菌。人类适应的先前证据已经通过长期携带免疫抑制患者以及与人类疾病相关的某些弯曲杆菌谱系 GBS 等慢性后遗症很少在人类宿主之外发现。我们已经确定了这些秘鲁亚马逊地区两项纵向队列研究的观察结果，总计超过 1400 项儿童年的监测、20,000 个粪便样本和 850 个弯曲杆菌分离株。具体来说，我们证明a）在 0 至 24 个月的完整随访中，超过 70% 的儿童存在持续的弯曲杆菌感染和携带， b) 与全球临床收集的空肠弯曲菌菌株相比，源自人类的高水平空肠弯曲菌菌株多样性基因组，c) 仅在人类宿主中描述的高比例菌株（例如 ST-403、ST2802 和 ST- 2993），与全球参考集合相比，d）人类基因组大小显着减小将衍生的空肠弯曲菌基因组与全球参考集合进行比较。为了检验我们的假设，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) 确定是否时空聚集性感染代表人与人之间的传播。拟议的项目将联合一个高度互补的团队，由在流行病学、进化论等方面具有丰富经验的研究人员组成生物学、弯曲杆菌基因组学和生物信息学为战略性和有针对性的疾病控制提供信息在人类耐多药率最高的地区之一控制弯曲菌的干预措施弯曲杆菌感染。 [该项目的创新之处在于应用微生物 GWAS 方法来利用基于源自明确定义的纵向队列研究的特殊菌株库，以有效识别宿主适应。] [这项研究产生的人类宿主适应的高质量证据将是范例转向控制弯曲杆菌的策略，并可能改变临床管理弯曲杆菌肠炎。]