title: FimH-mediated Escherichia coli K1 invasion of human brain microvascular endothelial cells.
abstract: Adhesion to brain microvascular endothelial cells, which constitute the blood-brain barrier is considered important in Escherichia coli K1 bacterial penetration into the central nervous system. Type 1 fimbriae are known to mediate bacterial interactions with human brain microvascular endothelial cells (HBMEC). Here, we demonstrate that type 1 fimbriae, specifically FimH adhesin is not only an adhesive organelle that provides bacteria with a foothold on brain endothelial cells but also triggers signalling events that promote E. coli K1 invasion in HBMEC. This is shown by our demonstrations that exogenous FimH increases cytosolic-free-calcium levels as well as activates RhoA. Using purified recombinant mannose-recognition domain of FimH, we identified a glycosylphosphatidylinositol-anchored receptor, CD48, as a putative HBMEC receptor for FimH. Furthermore, E. coli K1 binding to and invasion of HBMEC were blocked by CD48 antibody. Taken together, these findings indicate that FimH induces host cell signalling cascades that are involved in E. coli K1 invasion of HBMEC and CD48 is a putative HBMEC receptor for FimH.
authors.affiliation: Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 256, Baltimore, MD 21287, USA.
authors.forename: Naveed Ahmed
authors.initials: NA
authors.lastname: Khan
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
authors.forename: Sooan
authors.initials: S
authors.lastname: Shin
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000907:Antibodies, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D001422:Bacterial Adhesion; D001812:Blood-Brain Barrier / Q000166:cytology; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D000071178:CD48 Antigen; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D003600:Cytosol / Q000737:chemistry; D042783:Endothelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity*; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008358:Mannose / Q000378:metabolism; D010766:Phosphorylation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D018830:Adhesins, Escherichia coli; D000907:Antibodies, Bacterial; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D020742:rhoA GTP-Binding Protein; D008358:Mannose; D002118:Calcium