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.

尽管持续进行监测和控制工作，B 族链球菌 (GBS) 仍然是一种 是造成新生儿感染发病率和死亡率的重要原因，也是导致新生儿感染率不断上升的重要原因 成人侵袭性疾病的原因。 GBS 疫苗的开发是当务之急， 候选结合多糖疫苗目前正在进行人体试验。该疫苗针对六种 基于侵袭性疾病的流行病学研究以及 10 种已知 GBS 血清型 直肠阴道运输。血清型分布数据主要基于单菌落分析 来自临床样本。根据我们的初步数据，我们假设携带非 疫苗类型 (NVT) GBS（血清型 VI-IX）比以前更加常见 意识到了。此外，NVT GBS 引起的侵袭性感染的频率也在增加。它不是 已知不太常见的 GBS 血清型本质上是否比更常见的血清型更不适合 关于定植效率或致病性的问题。同样，重要性 最近鉴定出天然存在的“胶囊开关”GBS 菌株，其中遗传 决定荚膜类型的基因座已从一种菌株转移到另一种菌株，仍然存在 不完全理解。在这里，我们提出了一个旨在检验假设的研究计划 关于 NVT 引起的定植和侵袭性感染的流行率（及其危险因素） 人类样本中的 GBS 血清型以及使用新开发的 GBS 基因组技术 操作以了解特定荚膜和非荚膜因子在定植中的作用 体内健身与发病机制。