Equipe d'Accueil 3854 Bactéries et Risque Materno-Foetal, Institut Fédératif de Recherche 136 Agents Transmissibles et Infectiologie, UFR Médecine, Université François Rabelais de Tours, Tours, France.
PLoS One. 2010 May 24;5(5):e10794. doi: 10.1371/journal.pone.0010794.
Group B streptococcus (GBS) is the main cause of neonatal sepsis and meningitis. Bacterial surface proteins play a major role in GBS binding to and invasion of different host surfaces. The scpB and lmb genes, coding for fibronectin-binding and laminin-binding surface proteins, are present in almost all human GBS isolates. The scpB-lmb intergenic region is a hot spot for integration of two mobile genetic elements (MGEs): the insertion element IS1548 or the group II intron GBSi1. We studied the structure of scpB-lmb intergenic region in 111 GBS isolates belonging to the intraspecies major clonal complexes (CCs). IS1548 was mostly found (72.2%) in CC19 serotype III strains recovered more specifically (92.3%) from neonatal meningitis. GBSi1 was principally found (70.6%) in CC17 strains, mostly (94.4%) of serotype III, but also (15.7%) in CC19 strains, mostly (87.5%) of serotype II. No MGE was found in most strains of the other CCs (76.0%), notably CC23, CC10 and CC1. Twenty-six strains representing these three genetic configurations were selected to investigate the transcription and expression levels of scpB and lmb genes. Quantitative RT-PCR showed that lmb transcripts were 5.0- to 9.6-fold higher in the group of strains with IS1548 than in the other two groups of strains (P<0.001). Accordingly, the binding ability to laminin was 3.8- to 6.6-fold higher in these strains (P< or =0.001). Moreover, Lmb amount expressed on the cell surface was 2.4- to 2.7-fold greater in these strains (P<0.001). By contrast, scpB transcript levels and fibronectin binding ability were similar in the three groups of strains. Deletion of the IS1548 sequence between scpB and lmb genes in a CC19 serotype III GBS strain substantially reduced the transcription of lmb gene (13.5-fold), the binding ability to laminin (6.2-fold), and the expression of Lmb protein (5.0-fold). These data highlight the importance of MGEs in bacterial virulence and demonstrate the up-regulation of lmb gene by IS1548; the increased lmb gene expression observed in CC19 serotype III strains with IS1548 may play a role in their ability to cause neonatal meningitis and endocarditis.
B 群链球菌(GBS)是导致新生儿败血症和脑膜炎的主要原因。细菌表面蛋白在 GBS 与不同宿主表面的结合和入侵中起主要作用。scpB 和 lmb 基因,编码纤连蛋白结合和层粘连蛋白结合表面蛋白,存在于几乎所有的人类 GBS 分离株中。scpB-lmb 基因间区是两个移动遗传元件(MGEs)插入的热点:插入元件 IS1548 或组 II 内含子 GBSi1。我们研究了属于种内主要克隆群(CC)的 111 株 GBS 分离株的 scpB-lmb 基因间区结构。IS1548 主要存在于 CC19 血清型 III 菌株中(72.2%),特别是从新生儿脑膜炎中分离到的菌株(92.3%)。GBSi1 主要存在于 CC17 菌株中(70.6%),主要是血清型 III(94.4%),但也存在于 CC19 菌株中(15.7%),主要是血清型 II。其他 CC 的大多数菌株(76.0%)中没有发现 MGE,特别是 CC23、CC10 和 CC1。选择 26 株代表这三种遗传结构的菌株,以研究 scpB 和 lmb 基因的转录和表达水平。定量 RT-PCR 显示,携带 IS1548 的菌株中 lmb 转录物的水平比其他两组菌株高 5.0-9.6 倍(P<0.001)。相应地,这些菌株与层粘连蛋白的结合能力高 3.8-6.6 倍(P<0.001)。此外,这些菌株表面表达的 Lmb 量增加了 2.4-2.7 倍(P<0.001)。相比之下,三组菌株的 scpB 转录物水平和纤连蛋白结合能力相似。在 CC19 血清型 III GBS 菌株中缺失 scpB 和 lmb 基因之间的 IS1548 序列,大大降低了 lmb 基因的转录(13.5 倍)、与层粘连蛋白的结合能力(6.2 倍)和 Lmb 蛋白的表达(5.0 倍)。这些数据强调了 MGE 在细菌毒力中的重要性,并证明了 IS1548 对 lmb 基因的上调;在携带 IS1548 的 CC19 血清型 III 菌株中观察到的 lmb 基因表达增加可能在其引起新生儿脑膜炎和心内膜炎的能力中发挥作用。