Understanding of Streptococcus agalactiae virulence and disease mechanisms using comparative genomics and in vivo models

Group B Streptococcus (GBS) is a Gram-positive bacterium and a leading cause of sepsis and meningitis worldwide and is associated with high rates of mortality and morbidity, especially in infants. GBS is a commensal organism found in the intestinal and vaginal flora; however, under certain circumstances, it can spread into the systemic circulation and cause life-threatening invasive disease. In the newborn, the invasion process is believed to primarily occur via vertical transmission from a carrier mother during the delivery process. To date, ten distinct serotypes have been described based on their capsular polysaccharide composition. As is the case for other Gram-positive bacteria, the GBS capsule is a major virulence factor contributing to the evasion of phagocytosis. Other major virulence factors include haemolysin, C5a peptidase and serine protease, but their role in disease causation remains to be determined. Developing murine models of colonisation transmission and invasive disease is very important to understanding the mechanisms of known and unknown virulence factors. In this project, we seek to identify novel virulence regulators that may play a role in the transition of GBS from carriage to invasive disease.

B群链球菌（Group B Streptococcus, GBS）是一种革兰氏阳性菌，也是全球范围内引发败血症与脑膜炎的主要致病菌，其导致的死亡率与发病率居高不下，尤其对婴幼儿群体危害显著。GBS是定植于肠道与阴道菌群中的共生微生物，但在特定条件下可侵入体循环，引发危及生命的侵袭性感染。对于新生儿而言，该病菌的侵袭主要被认为是在分娩过程中通过携带病菌的母亲发生垂直传播所致。截至目前，依据荚膜多糖的结构组成，已鉴定出十种明确的血清型。与其他革兰氏阳性菌类似，GBS的荚膜是其主要毒力因子之一，可帮助菌体逃避宿主的吞噬作用。其他主要毒力因子还包括溶血素、C5a肽酶与丝氨酸蛋白酶，但它们在疾病致病过程中所发挥的作用仍有待进一步阐明。建立定植传播与侵袭性疾病的小鼠模型，对于解析已知与未知毒力因子的作用机制具有重要意义。本项目旨在鉴定可能参与GBS从定植状态向侵袭性疾病转化过程的新型毒力调控因子。