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

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

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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.]

抽象的人畜共患病原体弯曲杆菌的人类适应性有很大的流行病学证据。然而，这种适应的基因组特征尚未系统地评估。总体目标项目是确定与适应性有关的弯曲杆菌的特定基因组特征人类主持人的长期目标是将这些知识应用于全球参考数据库以告知主机归因和指导改进的疾病控制措施，减轻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，长期暴露允许适应人类宿主，而不是瞬态感染流行病学，我们通常会观察到弯曲杆菌。先前的人类适应性证据以前是通过长时间的运输来提出的免疫抑制的患者以及某些与人类疾病和慢性后遗症如GB，很少在人类宿主以外发现。我们已经确定了这些在秘鲁亚马逊的两项纵向队列研究中的观察，累计构成了1400多个监视儿童年，20,000个粪便样品和850个弯曲杆菌分离株。具体来说，我们证明A）超过70％的儿童持续的弯曲杆菌感染和运输，有0至24个月的随访， b）与全球临床收集相比基因组，c）在人类宿主中仅描述的菌株的高比例（例如ST-403，ST2802和ST-） 2993），与全球参考集合和d）相比与全球参考收集相比，衍生的空肠梭菌基因组。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，2）确定是否确定时空聚类感染代表人类传播。拟议的项目将团结起来一群具有流行病学专业知识的有成就的研究人员，进化论生物学，弯曲杆菌基因组学和生物信息学，以告知战略和有针对性的疾病控制在人类MDR率最高的区域之一中，弯曲杆菌控制的干预措施弯曲杆菌感染。 [该项目以应用微生物GWAS方法的方式具有创新性在从定义明确的纵向队列研究中得出的特殊应变库中，有效地识别宿主 [适应。] [本研究产生的人类宿主适应的高质量证据将是范式转移到用于控制弯曲杆菌的策略，可能会改变弯曲杆菌肠炎。]