Xie Yi, Parthasarathy Geetha, Di Cello Francescopaolo, Teng Ching-Hao, Paul-Satyaseela Maneesh, Kim Kwang Sik
Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 1109, Baltimore, MD 21205, USA.
Biochem Biophys Res Commun. 2008 Jan 4;365(1):201-6. doi: 10.1016/j.bbrc.2007.10.174. Epub 2007 Nov 5.
Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Binding to human brain microvascular endothelial cells (HBMEC) is an essential step for E. coli K1 traversal of the blood-brain barrier. In this study, we examined expression profiles of E. coli K1 strain RS218 during its binding to HBMEC. Comparison of HBMEC-bound E. coli K1 with collagen-bound E. coli revealed more than one hundred genes whose expression patterns were significantly changed in HBMEC-bound E. coli K1, but not in collagen-bound E. coli K1. These genes are involved mainly in cell surface decorations, cellular function, and nitrogen metabolism. The roles of several representative genes including frdA, clpB, carA, and ompT in HBMEC binding were verified with their isogenic mutants, which exhibited significantly less HBMEC binding capability compared to that of the parent strain. This transcriptome analysis provided us with the first genomic-level view of E. coli and HBMEC interactions.
大肠杆菌K1是引起新生儿脑膜炎最常见的革兰氏阴性菌。与人类脑微血管内皮细胞（HBMEC）结合是大肠杆菌K1穿越血脑屏障的关键步骤。在本研究中，我们检测了大肠杆菌K1菌株RS218与HBMEC结合过程中的表达谱。将与HBMEC结合的大肠杆菌K1和与胶原蛋白结合的大肠杆菌进行比较，发现有一百多个基因的表达模式在与HBMEC结合的大肠杆菌K1中发生了显著变化，而在与胶原蛋白结合的大肠杆菌K1中未发生变化。这些基因主要参与细胞表面修饰、细胞功能和氮代谢。通过构建包括frdA、clpB、carA和ompT在内的几个代表性基因的同基因突变体，验证了它们在与HBMEC结合中的作用，这些突变体与亲本菌株相比，与HBMEC结合的能力显著降低。这项转录组分析为我们提供了大肠杆菌与HBMEC相互作用的首个基因组水平视角。
