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

• 批准号: 10297242
• 负责人: Adam Jonathan Ratner
• 金额: $ 71.02万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-08 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10297242
• 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

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.

尽管正在进行监测和控制工作，B组链球菌（GBS）仍然是一个流行病。 这是新生儿感染发病率和死亡率的重要原因， 成人侵袭性疾病的原因。GBS疫苗开发是一个高度优先事项， 候选的结合多糖疫苗目前正在人体试验中。该疫苗针对6个 在10种已知的GBS血清型中，基于侵袭性疾病的流行病学研究以及 直肠阴道分娩血清型分布数据主要基于单菌落的测定 从临床样本中。根据我们的初步数据，我们假设携带非- 疫苗型（NVT）GBS（血清型VI-IX）比以前更常见 实现了此外，由于NVT GBS引起的侵袭性感染的频率正在增加。不 已知较不常见的GBS血清型是否本质上不如较常见的GBS血清型适合 关于定殖效率或致病性。同样， 最近表征的天然存在的“胶囊开关”GBS菌株，其中遗传 决定荚膜类型的基因座从一个菌株转移到另一个菌株， 不完全理解。在这里，我们提出了一个研究计划，旨在测试假设 关于NVT引起的定植和侵袭性感染的患病率（和风险因素） GBS血清型检测和GBS基因组检测的新技术 操作以了解特定包膜和非包膜因子在定植中的作用 适应性和致病性。