Genetic Diversity and Molecular Epidemiology of GBS

GBS 的遗传多样性和分子流行病学

• 批准号: 7074677
• 负责人: HERBERT D DAVIES
• 金额: $ 29.49万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7074677
• 关键词: Streptococcus agalactiae; Streptococcus infection; antibiotics; bacterial genetics; clinical research; epidemiology; gene expression profiling; genetic strain; human data; human tissue; microorganism disease chemotherapy; rectum /anus; vagina; virulence

DESCRIPTION (provided by applicant): Group B Streptococcus (GBS) is the primary cause of invasive infections (e.g., bacteremia and meningitis) in newborns and pregnant women and an increasingly important cause of disease in the elderly. While a lot of attention has recently been focused on the discovery of GBS virulence genes, little is known about the contributions and interactions between them towards the pathogenicity of GBS. We propose a detailed molecular epidemiologic study of invasive and maternal colonizing isolates obtained from prospective population-based surveillance and two pregnancy- related cohort studies conducted in the Province of Alberta, Canada (population approximately 2.8 million) over an eight-year period. Specific Aim1: To characterize the clonal relationships and multiple virulence gene profiles of invasive GBS in a population based study. Specific Aim 2: To compare differences in the virulence gene profiles between colonizing vaginal-rectal derived GBS isolates and invasive isolates. Specific Aim 3: To investigate the impact of the delivery process and antibiotic treatment on the clonal composition and antigenic diversity of GBS colonizing the vaginal-rectal tract. Our ability to use GBS isolates from a population based study to identify specific virulence genes, virulence gene profiles, and certain clonal types that are associated with both colonization and clinical disease would greatly improve our understanding of the pathogenesis of invasive GBS disease. It will also aid in epidemiological studies to establish relationships between strains and determine what role if any specific phenotypes should play in vaccine development. In addition, the assessment of colonizing GBS strains will provide fundamental insights into the nature of GBS colonization, which is the critical first step preceding neonatal transmission, infection and disease.

描述（由申请人提供）：B组链球菌（GBS）是新生儿和孕妇的侵入性感染（例如菌血症和脑膜炎）的主要原因，也是老年人疾病越来越重要的原因。尽管最近有很多关注集中在发现GBS毒力基因的发现上，但对它们之间对GBS致病性的贡献和相互作用知之甚少。我们提出了一项详细的分子流行病学研究，对在八年内在加拿大艾伯塔省（大约280万）进行的前瞻性人群监测和两项与妊娠相关的同类研究获得的侵入性和孕产妇定植分离株和两项相关的同类研究。特定目标1：在基于人群的研究中表征侵入性GB的克隆关系和多重毒力基因谱。特定目的2：比较定植阴道直肠衍生的GBS分离株和浸润性分离株之间毒力基因谱的差异。特定目的3：研究递送过程和抗生素处理对GBS的克隆组成和抗原多样性的影响，使阴道直肠界定居。我们使用基于人群研究的GBS分离株来鉴定特定的毒力基因，毒力基因谱以及某些与定殖和临床疾病相关的克隆类型的能力将大大提高我们对侵入性GBS疾病发病机理的理解。它还将有助于流行病学研究建立菌株之间的关系，并确定是否应在疫苗开发中发挥任何特定表型的作用。此外，对GBS菌株定居的评估将提供对GBS定殖本质的基本见解，GBS定植是新生儿传播，感染和疾病之前的关键第一步。