Modelling streptococcal urogenital tract infection to study mechanisms of bacterial colonization and persistence

建立链球菌泌尿生殖道感染模型以研究细菌定植和持续存在的机制

• 批准号: nhmrc : 455901
• 负责人: Prof Glen Ulett
• 金额: $ 27.48万
• 依托单位: Griffith University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/modelling-streptococcal-urogenital-colonization-persistence/99233
• 关键词: Modelling; streptococcal; urogenital; tract; infection

Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infections and neonatal infections resulting from vertical transmission of colonizing bacteria from mothers to newborns. Aside from sexually-transmitted diseases the most prominent bacterial pathogens that colonize the urogenital tract are Group B Streptococcus (GBS) and Escherichia coli. GBS in particular exist in the female urogenital tract as a persistent microbial reservoir in up to 40% of pregnant women and are transmitted to newborns in up to 72% of live births. Colonization of newborns leads to invasive disease including pneumonia, sepsis, and meningitis. While the disease presentations resulting from colonization of the urogenital tract vary the underlying basis that leads to disease is antecedent bacterial persistence in the urogenital tract despite immune system activation. The mechanisms whereby GBS evade immune responses in the urogenital tract to allow their survival are unknown. I will define the immune-evasion mechanisms and virulence traits used by GBS, as a model urogenital pathogen, to successfully colonize the urogenital tract in the face of mounting immune responses. These studies will provide a better understanding of the pathogenesis of urogenital disease in terms of bacterial colonization and immune-evasion strategies. This will shed light onto new approaches for the prevention and treatment of urogenital disease in humans such as improved vaccination, locally acting cytokines, and deliberate colonization with non-invasive strains for the prevention of disease.

细菌病原体在泌尿生殖道的定植是人类最常见的感染之一。在澳大利亚，数百万人在任何给定时间在其泌尿生殖道中定植，通常是无症状的，并且许多这样的个体需要医疗干预以治疗由持续定植导致的后续感染。泌尿生殖道的细菌定殖与多种疾病表现相关，包括尿路感染和由定殖细菌从母亲到新生儿的垂直传播引起的新生儿感染。除了性传播疾病外，最突出的细菌病原体是定植在泌尿生殖道的B族链球菌（GBS）和大肠杆菌。GBS特别存在于女性泌尿生殖道中，作为高达40%的孕妇的持久性微生物储存库，并在高达72%的活产婴儿中传播给新生儿。新生儿的定植导致侵袭性疾病，包括肺炎、败血症和脑膜炎。虽然由泌尿生殖道定植引起的疾病表现各不相同，但导致疾病的潜在基础是尽管免疫系统激活，但泌尿生殖道中的前驱细菌持续存在。GBS逃避泌尿生殖道免疫反应以使其存活的机制尚不清楚。我将定义GBS作为泌尿生殖道病原体的模型，在面对越来越多的免疫反应时成功地在泌尿生殖道定植的免疫逃避机制和毒力特征。这些研究将提供一个更好的了解泌尿生殖系统疾病的发病机制方面的细菌定植和免疫逃避策略。这将揭示预防和治疗人类泌尿生殖系统疾病的新方法，例如改进疫苗接种，局部作用细胞因子以及使用非侵入性菌株进行故意定殖以预防疾病。