Department of Pediatric Infectious Diseases and 2 Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195.
J Exp Med. 2013 Jun 3;210(6):1265-81. doi: 10.1084/jem.20122753. Epub 2013 May 27.
Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury.
羊水微生物感染是胎儿损伤、早产和新生儿感染的重要原因。B 群链球菌（GBS）是一种与早产、胎儿损伤和新生儿死亡率相关的重要人类细菌病原体。尽管 GBS 已从早产妇女的羊水中分离出来，但宫内感染的机制仍不清楚。先前的研究表明，GBS 无法侵入人羊膜上皮细胞（hAECs），hAECs 是羊膜腔和胎儿的最后一道屏障。我们发现 GBS 可侵入 hAECs，且缺乏溶血素抑制剂 CovR/S 的菌株可通过溶血素依赖性方式加速羊膜屏障失效并穿透绒毛膜羊膜炎。从早产妇女中获得的临床 GBS 分离株具有高溶血活性，其中一些与 covR/S 突变相关。我们首次证明，GBS 的溶血性和细胞溶解性活性归因于鸟氨酸鼠李糖脂色素，而不是由于形成孔的蛋白毒素。我们的研究强调了溶血 GBS 色素在向上感染和胎儿损伤中的重要性。
