Genomics of Salmonella Typhi in Samoa: Population structure and genomic epidemiology

萨摩亚伤寒沙门氏菌基因组学：种群结构和基因组流行病学

• 批准号: 10398814
• 负责人: Michael Joseph Sikorski
• 金额: $ 3.72万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10398814
• 关键词: Acute; Age; Age-Years; Antibiotic Resistance; Bacteremia; Bacteria; Bacterial Infections; Bile fluid; Biliary; Blood; Blood Circulation; Bone Marrow; Cholelithiasis; Chronic; Cities; Clinical; Collaborations; Collection; Communicable Diseases; Comparative Genomic Analysis; Consumption; Country; Data; Disease; Disease Outbreaks; Disease model; Duodenum; Environment; Environmental Risk Factor; Epidemiology; Etiology; Evolution; Exhibits; Family member; Female; Filtration; Flushing; Food Contamination; Fostering; Founder Effect; Funding; Gallbladder; Genes; Genome; Genomic Segment; Genomics; Genotype; Geography; Goals; Health; Hepatobiliary; Household; Human; Incidence; Individual; Infection; Institutes; International; Intestinal Mucosa; Intestines; Investigation; Island; Link; Liquid substance; Liver; Methods; Modeling; Modernization; Molecular; Mononuclear; Obesity; Pacific Islands; Pattern; Persons; Phagocytes; Phylogenetic Analysis; Phylogeny; Policies; Polynesian; Population; Prevalence; Public Health; Recording of previous events; Relapse; Resolution; Risk; Risk Factors; Role; Salmonella typhi; Samoa; Samoan; Sanitation; Sepsis; Series; Silicon Dioxide; Single Nucleotide Polymorphism; Source; Spleen; Structure; System; Systemic infection; Technology; Testing; Time; Training; Trees; Typhoid Fever; Variant; Virulence Factors; Water; Water Supply; bacterial genome sequencing; base; chlorination; comparative genomics; contaminated water; epidemiologic data; extensive drug resistance; food consumption; genome sequencing; genomic epidemiology; improved; lymphatic drainage; macrophage; programs; resistance factors; septic; spatiotemporal; tool; transmission process; water quality; waterborne; whole genome

Project Summary / Abstract Samoa is an island nation in the South Pacific (population ~200,000). For decades and despite improved water quality and sanitation, Samoans have faced endemic typhoid fever, a potentially fatal human host-restricted bacterial infection of the blood, hepatobiliary tree, and intestine caused by Salmonella enterica serovar Typhi (S. Typhi). We recently described the epidemiology of endemic typhoid fever in Samoa by person, place, and time (Sikorski et al., accepted, Clinical Infectious Diseases, 2020), but the mechanisms sustaining transmission – either direct spread or indirect environmental amplification – remain unknown. Bacterial whole genome sequencing (WGS) is a modern molecular tool that can establish phylogenetic relationships, test for antibiotic resistance and virulence factors, as well as detect outbreaks. Paired with high resolution epidemiologic and geospatial data (i.e., data generated by the Samoa Typhoid Fever Surveillance Initiative) WGS can help to explain origins, evolution, clustering, and transmission patterns. Our long-term goals are to examine the genomic population structure and evolution of S. Typhi circulating in Samoa using WGS and to combine comparative genomics with geospatial epidemiology to help explain its endemicity. Large-scale genomic studies describe the emergence and global spread of aggressive extensively-drug resistant S. Typhi strains, but none have focused on Samoa. The genomics S. Typhi in Samoa not known nor is the date or geographical source of introduction. Our preliminary WGS analyses of 176 S. Typhi isolates from Samoa from 1992-2018 show (i) an exclusive Samoan genotype that appears nowhere else in the world, (ii) geospatial clustering of genomically related isolates, and (iii) the presence of unique genes found only in the Samoan isolates. We hypothesize that a unique strain of S. Typhi entered Samoa decades ago and expanded into the dominant circulating strain, and asymptomatic chronic gallbladder carriers of the strain serve as an effective long-term reservoir and source of infection. We propose two Specific Aims: (1) characterize the genomics of S. Typhi causing clinical disease in Samoa, and (2) define the role of asymptomatic S. Typhi carriers (N=24 to date) using combined WGS and geospatial analyses. Isolates from Samoa will be sequenced and assembled and then compared with the global collection of S. Typhi (~3,400 isolates) using single nucleotide polymorphism and Bayesian evolutionary phylogenetic analyses. We will apply our lab's large-scale blast score ratio pipeline to identify any new and/or deleted genes. After funded training from the Institute for Disease Modeling we will combine the data on genomic relatedness among S. Typhi isolates with clinical, epidemiologic, and geospatial data to demonstrate local patterns of transmission. These detailed analyses have never been completed on Samoan S. Typhi, and the results will be integrated into public health decisions and policies.

项目摘要 /摘要 萨摩亚是南太平洋的一个岛国（人口约20,000）。数十年来，欲望改善了水 质量和卫生，萨摩亚人面临内在伤寒，这是一种潜在的致命人类宿主受限的 由沙门氏菌typhi引起的血液，肝小树和肠道的细菌感染 （S. Typhi）。我们最近描述了萨摩亚人，地点和地方的内在伤寒的流行病学 时间（Sikorski等人，被接受，临床传染病，2020年），但是持续传播的机制 - 直接传播或间接的环境扩增 - 仍然未知。细菌整体基因组 测序（WGS）是一种现代的分子工具，可以建立系统发育关系，测试抗生素 抗性和病毒因素以及检测暴发。与高分辨率流行病学和 地理空间数据（即，萨摩亚伤寒监测计划生成的数据）WGS可以帮助有助于 解释起源，进化，聚类和传播模式。我们的长期目标是检查 使用WGS在Samoa中循环的鼠疫链球菌的基因组种群结构和演变 与地理空间流行病学的比较基因组学有助于解释其内在。大规模基因组 研究描述了积极的广泛抗药性链球菌菌株的出现和全球传播， 但是没有人专注于萨摩亚。萨摩亚中的基因组学链球菌尚不清楚，日期或地理 介绍来源。我们从1992 - 2018年对Samoa的176次鼠伤寒S. Typhi分离株进行了初步WGS分析 展示（i）独家萨摩亚基因型，在世界上没有其他任何地方，（ii）地理空间聚类 基因组相关的分离株，（iii）仅在萨摩亚分离株中发现的独特基因的存在。我们 假设几十年前进入萨摩亚的独特菌株进入了萨摩亚，并扩展为主要 菌株的循环应变和不对称的慢性胆囊载体作为有效的长期 水库和感染的来源。我们提出了两个具体的目的：（1）表征了鼠伤寒的基因组学 引起萨摩亚的临床疾病，（2）定义了无症状的鼠伤寒沙门氏菌的作用（迄今n = 24） 使用联合WGS和地理空间分析。来自萨摩亚的分离株将进行测序和组装，并且 然后与使用单个核苷酸多态性的全球鼠伤寒（〜3,400个分离株）进行比较 和贝叶斯进化系统发育分析。我们将应用实验室的大规模爆炸比率管道 识别任何新的和/或已删除的基因。经过疾病建模研究所的资助培训，我们将 结合链球菌分离株之间基因组相关性的数据与临床，流行病学和地理空间 数据以证明局部传输模式。这些详细的分析从未完成 Samoan S. Typhi，结果将纳入公共卫生决策和政策。