Capsular serotype in group B Streptococcus colonization and disease

B 组链球菌定植和疾病中的荚膜血清型

基本信息

批准号：
10424581
负责人：
Adam Jonathan Ratner
金额：
$ 70.25万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-08 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10424581
关键词：
Address Adult Alleles Animal Model Antibiotics Bacterial Genes Biological Assay Biology Centers for Disease Control and Prevention (U.S.)Characteristics Clinical Conjugate Vaccines Data Disease Epidemiology Etiology Frequencies Genes Genetic Genome Genomics Goals Human Infant Infection Laboratories Metadata Morbidity - disease rate Mutation Neonatal Newborn Infant Pathogenesis Pathogenicity Polysaccharides Population Pregnant Women Prevalence Prevention Prophylactic treatment Prospective Studies Research Research Design Risk Risk Factors Role Sampling Serotyping Streptococcal Infections Streptococcus Group B System Techniques Testing Vaccination Vaccines antimicrobial bacterial genetics base capsule comparative cost epidemiology study fitness genome sequencing genomic locus in vivo intrapartum mortality mouse model mutant neonatal sepsis programs screening screening program success tool vaccine candidate vaccine development whole genome

项目摘要

Despite ongoing surveillance and control efforts, group B Streptococcus (GBS) remains an important cause of infectious morbidity and mortality among newborns, as well as an increasing cause of invasive disease in adults. GBS vaccine development is a high priority, and a candidate conjugate polysaccharide vaccine is currently in human trials. This vaccine targets six of the ten known GBS serotypes, based on epidemiologic studies of invasive disease as well as rectovaginal carriage. Serotype distribution data are largely based on assays of single colonies from clinical samples. Based on our preliminary data, we hypothesize that carriage of non- vaccine type (NVT) GBS (serotypes VI-IX) is substantially more common than previously realized. Additionally, invasive infections due to NVT GBS are increasing in frequency. It is not known whether the less common GBS serotypes are intrinsically less fit than the more common ones with respect to colonization efficiency or pathogenicity. Likewise, the importance of recently characterized naturally occurring "capsule switch" GBS strains, in which the genetic locus that determines capsular type has transferred from one strain to another, remains incompletely understood. Here we propose a program of research designed to test hypotheses regarding the prevalence of (and risk factors for) colonization and invasive infection due to NVT GBS serotypes in human samples and to use newly developed techniques for GBS genome manipulation to understand the role of specific capsule and non-capsule factors in colonization fitness and pathogenesis in vivo.

尽管进行了持续的监视和控制工作，但B组链球菌（GBS）仍然是新生儿感染性发病和死亡率的重要原因，以及增加成人侵入性疾病的原因。 GBS疫苗开发是高度优先级，A 候选共轭多糖疫苗目前正在人类试验中。该疫苗靶向六个基于侵入性疾病的流行病学研究以及十种已知的GBS血清型直流马车。血清型分布数据主要基于单个菌落的测定来自临床样品。根据我们的初步数据，我们假设非 - 疫苗类型（NVT）GBS（血清型VI-IX）比以前更常见实现。另外，由于NVT GBS引起的侵入性感染的频率正在增加。它不是知道较不常见的GBS血清型本质上是否比更常见关于定殖效率或致病性的。同样，重要性最近表征了天然存在的“胶囊开关” GBS菌株，其中遗传确定囊类型的基因座已从一个菌株转移到另一种菌株，仍然存在不完全理解。在这里，我们提出了一项旨在检验假设的研究计划关于NVT引起的定植和侵入性感染的患病率（和风险因素）人类样品中的GBS血清型，并使用新开发的GBS基因组技术操纵以了解特定胶囊和非胶囊因子在定植中的作用体内适应性和发病机理。