Outer membrane protein A of Escherichia coli contributes to invasion of brain microvascular endothelial cells
Outer membrane protein A of Escherichia coli contributes to invasion of brain microvascular endothelial cells
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DOI：
10.1128/iai.64.1.146-153.1996
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发表时间：
1996-01-01
影响因子：
3.1
通讯作者：
Kim, KS
中科院分区：
文献类型：
--
作者：
Prasadarao, NV;Wass, CA;Kim, KS
大肠杆菌是引起新生儿脑膜炎的最常见的革兰氏阴性菌，但目前尚不清楚是什么微生物因素介导了大肠杆菌的传播。大肠杆菌穿过血脑屏障外膜蛋白A（OmpA）是一种高度保守的35 kDa蛋白，它在大肠杆菌中的作用被研究。coli K1对脑微血管内皮细胞（BMEC）的侵袭作用。OmpA（+）菌株的侵袭能力是OmpA（-）菌株的25- 50倍，并且OmpA（-）菌株的侵袭能力通过与OmpA基因互补而恢复到OmpA（+）菌株的水平。纯化的OmpA蛋白和多克隆抗体可抑制OmpA（+）E的侵袭。coli转化BMEC。由OmpA N端氨基酸序列合成的两个短肽（六聚体Asn-27-Glu-32和五聚体Gly-65-Asn-69）对OmpA（+）E具有显著的抑制作用。这两个序列分别代表了大肠杆菌的OmpA结构域。大肠杆菌侵袭BMEC。这些发现表明OmpA是第一个被鉴定为增强E.大肠杆菌侵袭BMEC是大肠杆菌致病过程中的重要事件。大肠杆菌脑膜炎。
Escherichia coli is the most common gram-negative bacteria causing meningitis during the neonatal period, but it is unclear what microbial factors mediate traversal of E. coli across the blood-brain barrier. Outer membrane protein A (OmpA), a highly conserved 35-kDa protein, was examined for its role in E. coli K1 invasion of brain microvascular endothelial cells (BMEC). The invasive capability of the OmpA(+) strains was 25- to 50-fold greater than that of OmpA(-) strains, and the invasive capability of OmpA(-) strains was restored to the level of the OmpA(+) strain by complementation with the ompA gene. Purified OmpA proteins and polyclonal anti-OmpA antibodies inhibited the invasion of OmpA(+) E. coli into BMEC. Two short synthetic peptides (a hexamer, Asn-27-Glu-32, and a pentamer, Gly-65-Asn-69) generated from the N-terminal amino acid sequence of OmpA exhibited significant inhibition of OmpA(+) E. coli invasion, suggesting that these two sequences represent the OmpA domains involved in E. coli invasion of BMEC. These findings suggest that OmpA is the first microbial structure identified to enhance E. coli invasion of BMEC, an important event in the pathogenesis of E. coli meningitis.