title: Escherichia coli K1-induced cytopathogenicity of human brain microvascular endothelial cells.
abstract: Pathophysiology of Escherichia coli sepsis is complex involving circulating bacterial products, cytokine release, and sustained bacteremia resulting in the damage of vascular endothelium. Here, it is shown that E. coli K1 produced cytopathogenicity of human brain microvascular endothelial cells (HBMEC), that constitute the blood-brain barrier. Whole bacteria or their conditioned medium produced severe HBMEC damage suggesting E. coli K1-cytopathogenicity is a contact-independent process. Using lipopolysaccharide (LPS) inhibitor, polymyxin B, purified LPS extracted from E. coli K1 as well as LPS mutant derived from E. coli K1, we showed that LPS is not the sole determinant of E. coli K1-mediated HBMEC death. Bacterial product(s) for HBMEC cytopathogenicity was heat-labile suggesting LPS-associated proteins. Several isogenic gene-deletion mutants (ΔompA, ΔibeA, ΔibeB, Δcnf1) exhibited HBMEC cytopathogenicity similar to that produced by wild type E. coli K1. E. coli K1-mediated HBMEC death was independent of phosphatidylinositol 3-kinase (PI3K) but dependent partially on focal adhesion kinase (FAK) using HBMEC expressing dominant negative FAK and PI3K.
authors: Department of Biological and Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan. Naveed5438@gmail.com
authors: Naveed Ahmed
authors: NA
authors: Khan
authors: Junaid
authors: J
authors: Iqbal
authors: Ruqaiyyah
authors: R
authors: Siddiqui
mesh_terms: D000942:Antigens, Bacterial; D016667:Bacterial Capsules / Q000737:chemistry / Q000378:metabolism*; D001921:Brain; D016923:Cell Death; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D006358:Hot Temperature; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D011135:Polysaccharides, Bacterial; D055550:Protein Stability / Q000528:radiation effects
chemical_list: D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; C036962:capsular polysaccharide K1