title: E-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae (Pnc) binds to nasopharyngeal (NP) epithelial cells in the first steps of nasopharyngeal carriage and colonization through bacterial adhesins. The pneumococcal surface adhesin A (PsaA) has previously been reported to play a significant role in pneumococcal adherence and colonization. Identification of a receptor for PsaA on human epithelium will aid in understanding the pathogenesis of this bacterium. Using recombinant PsaA covalently bound to fluorescent spheres (fluospheres), we show PsaA binds to NP cells through interaction with the human cellular receptor, E-cadherin. SDS-PAGE silver stain analysis demonstrates binding of PsaA to E-cadherin. Recombinant human E-cadherin binds to and blocks PsaA-coated fluospheres and whole transparent bacteria from adhering to NP cells, but does not block a Pnc PsaA(-) mutant. Recombinant E-selectin and human alpha(5)beta(1) integrin did not bind to or block PsaA-coated fluosphere adherence to NP cells. Likewise, if NP cells were preincubated with anti-E-cadherin antibody, there was a significant decrease (46%, P=0.05) in PsaA-coated fluosphere adherence to the cells. Additionally, when using E-cadherin transfected cells, we observed PsaA-coated fluospheres bind more efficiently to cells which express E-cadherin. This work identifies E-cadherin as a receptor on human epithelial cells for the pneumococcal surface adhesin, PsaA.
authors.affiliation: Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Bldg 18-B104, M/S G-05, Atlanta, GA 30333, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Anderton
authors.forename: Gowrisankar
authors.initials: G
authors.lastname: Rajam
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Steiner
authors.forename: Susan
authors.initials: S
authors.lastname: Summer
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Kowalczyk
authors.forename: George M
authors.initials: GM
authors.lastname: Carlone
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Sampson
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Ades
mesh_terms: D018829:Adhesins, Bacterial / Q000096:biosynthesis / Q000378:metabolism*; D001422:Bacterial Adhesion / Q000502:physiology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004492:Edetic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D006801:Humans; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D009305:Nasopharynx / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D011008:Pneumococcal Infections / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D014162:Transfection
chemical_list: D018829:Adhesins, Bacterial; D015820:Cadherins; D008074:Lipoproteins; C085000:PsaA protein, Streptococcus; D004492:Edetic Acid; D002118:Calcium