PDF(Pubmed)
Abstract：
The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3β1 and α2β1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3β1 and anti-α2β1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3β1 and α2β1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3β1 and α2β1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.
摘要：
肠道是共生细菌无乳链球菌（B组链球菌或GBS）定植的重要部位，在新生儿和成人中也可以表现为致命的病原体。肠上皮屏障的侵入可能是由属于克隆复合物17（CC17）的GBS引起的新生儿感染发病机理中的关键步骤。我们先前已经证明，原型CC17BM110菌株使用内吞途径通过其侧面侵入极化的肠上皮细胞样细胞。通过分析假定的GBS受体在人肠上皮细胞样Caco-2细胞中的细胞分布，我们在这里发现，α3（α3）和α2（α2）整联蛋白亚基在赤道和鼻旁水平的侧肠上皮细胞表面上沿着极化细胞的垂直轴选择性表达，在对应于GBS入口站点的区域中。在完全分化的Caco-2单层中，α3β1和α2β1整联蛋白不易获得，但在无钙培养基中削弱细胞间连接后，可以暴露于特定抗体。在这些条件下,抗α3β1和抗α2β1抗体显着降低GBS对肠细胞的粘附和侵袭。胞吞后,α3β1和α2β1整联蛋白定位于含有液泡的GBS周围的肌动蛋白重塑区域。一起来看,这些数据表明，GBS可以通过与极化肠细胞侧膜上的α3β1和α2β1整合素结合来侵入肠细胞，导致细胞骨架重塑和细菌内化。阻断整合素可能是防止GBS侵袭肠上皮组织的可行策略。
