Khursigara C, Abul-Milh M, Lau B, Girón J A, Lingwood C A, Barnett Foster D E
Department of Chemistry, Biology and Chemical Engineering, Ryerson University, Toronto, Ontario, Canada.
Infect Immun. 2001 Nov;69(11):6573-9. doi: 10.1128/IAI.69.11.6573-6579.2001.
The bundle-forming pilus (BFP) of enteropathogenic Escherichia coli (EPEC), an established virulence factor encoded on the EPEC adherence factor (EAF) plasmid, has been implicated in the formation of bacterial autoaggregates and in the localized adherence of EPEC to cultured epithelial cells. While understanding of the pathogenic mechanism of this organism is rapidly improving, a receptor ligand for BFP has not yet been identified. We now report, using both solid-phase and liposome binding assays, that BFP expression correlates with phosphatidylethanolamine (PE) binding. In a thin-layer chromatogram overlay assay, specific recognition of PE was documented for BFP-expressing strains, including E2348/69, a wild-type EPEC clinical isolate, as well as a laboratory strain, HB101, transformed with a bfp-carrying plasmid. Strains which did not express BFP did not bind PE, including a bfpA disruptional mutant of E2348/69, EAF plasmid-cured E2348/69, and HB101. E2348/69 also aggregated PE-containing liposomes but not phosphatidylcholine- or phosphatidylserine-containing liposomes, while BFP-negative strains did not produce aggregates with any tested liposomes. Purified BFP preparations bound commercial PE standards as well as a PE-containing band within lipid extracts from human epithelial cells and from E2348/69. Our results therefore indicate a specific interaction between BFP and PE and suggest that PE may serve as a BFP receptor for bacterial autoaggregation and may promote localized adherence to host cells, both of which contribute to bacterial pathogenesis.
肠致病性大肠杆菌(EPEC)的束状菌毛(BFP)是一种已确定的毒力因子,由EPEC黏附因子(EAF)质粒编码,与细菌自身聚集的形成以及EPEC对培养的上皮细胞的局部黏附有关。虽然对这种生物体致病机制的理解正在迅速提高,但尚未确定BFP的受体配体。我们现在报告,使用固相和脂质体结合试验,BFP的表达与磷脂酰乙醇胺(PE)结合相关。在薄层层析图覆盖试验中,记录到表达BFP的菌株,包括野生型EPEC临床分离株E2348/69以及用携带bfp的质粒转化的实验室菌株HB101,对PE有特异性识别。不表达BFP的菌株不结合PE,包括E2348/69的bfpA缺失突变体、EAF质粒治愈的E2348/69以及HB101。E2348/69还能使含PE的脂质体聚集,但不能使含磷脂酰胆碱或磷脂酰丝氨酸的脂质体聚集,而BFP阴性菌株与任何测试的脂质体都不产生聚集。纯化的BFP制剂能结合商业PE标准品以及来自人上皮细胞和E2348/69的脂质提取物中的一条含PE的条带。因此,我们的结果表明BFP与PE之间存在特异性相互作用,并提示PE可能作为BFP受体参与细菌自身聚集,并可能促进对宿主细胞的局部黏附这两者都有助于细菌致病。