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

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，任何时候都有数以百万计的人在其泌尿生殖道中被定植，通常是无症状的，许多这样的人需要医疗干预，以治疗由于持续定植而导致的后续感染。细菌在泌尿生殖道的定植与多种疾病有关，包括由定植细菌从母亲向新生儿垂直传播引起的尿路感染和新生儿感染。除了性传播疾病外，寄居在泌尿生殖道的最突出的细菌病原体是B族链球菌（GBS）和大肠杆菌。GBS尤其存在于女性泌尿生殖道中，在高达40%的孕妇中作为一个持久的微生物库存在，并在高达72%的活产中传播给新生儿。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，但泌尿生殖道中先前的细菌持续存在。GBS逃避泌尿生殖道免疫应答从而存活的机制尚不清楚。我将定义GBS的免疫逃避机制和毒力特征，作为一种模型泌尿生殖道病原体，在面对不断增加的免疫反应时成功地定殖泌尿生殖道。这些研究将在细菌定植和免疫逃避策略方面更好地了解泌尿生殖疾病的发病机制。这将揭示预防和治疗人类泌尿生殖疾病的新方法，如改进疫苗接种，局部作用的细胞因子，以及故意定植非侵入性菌株以预防疾病。

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.