title: Cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells.
abstract: The tetraspanins are a superfamily of transmembrane proteins with diverse functions and can form extended microdomains within the plasma membrane in conjunction with partner proteins, which probably includes receptors for bacterial adhesins. Neisseria meningitidis, the causative agent of meningococcal disease, attaches to host nasopharyngeal epithelial cells via type IV pili and opacity (Opa) proteins. We examined the role of tetraspanin function in Neisseria meningitidis adherence to epithelial cells. Tetraspanins CD9, CD63, and CD151 were expressed by HEC-1-B and DETROIT 562 cells. Coincubation of cells with antibodies against all three tetraspanin molecules used individually or in combination, with recombinant tetraspanin extracellular domains (EC2), or with small interfering RNAs (siRNAs) significantly reduced adherence of Neisseria meningitidis. In contrast, recombinant CD81, a different tetraspanin, had no effect on meningococcal adherence. Antitetraspanin antibodies reduced the adherence to epithelial cells of Neisseria meningitidis strain derivatives expressing Opa and pili significantly more than isogenic strains lacking these determinants. Adherence to epithelial cells of strains of Staphylococcus aureus, Neisseria lactamica, Escherichia coli, and Streptococcus pneumoniae was also reduced by pretreatment of cells with tetraspanin antibodies and recombinant proteins. These data suggest that tetraspanins are required for optimal function of epithelial adhesion platforms containing specific receptors for Neisseria meningitidis and potentially for multiple species of bacteria.
authors.affiliation: Department of Infection and Immunity, University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom.
authors.forename: Luke R
authors.initials: LR
authors.lastname: Green
authors.forename: Peter N
authors.initials: PN
authors.lastname: Monk
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Partridge
authors.forename: Paul
authors.initials: P
authors.lastname: Morris
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gorringe
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008585:Meningitis, Meningococcal / Q000382:microbiology; D008856:Microscopy, Fluorescence; D042806:Neisseria lactamica / Q000502:physiology; D009345:Neisseria meningitidis / Q000502:physiology; D016870:Neisseriaceae Infections / Q000382:microbiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D011008:Pneumococcal Infections / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000502:physiology; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D060149:Tetraspanin 30
chemical_list: D018829:Adhesins, Bacterial; D015703:Antigens, CD; C554715:CD151 protein, human; C554586:CD63 protein, human; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D060149:Tetraspanin 30