TY - JOUR
T1 - E-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae
AU - Anderton, Julie M.
AU - Rajam, Gowrisankar
AU - Romero-Steiner, Sandra
AU - Summer, Susan
AU - Kowalczyk, Andrew P.
AU - Carlone, George M.
AU - Sampson, Jacquelyn S.
AU - Ades, Edwin W.
N1 - Funding Information:
This research was supported in part by an appointment of J.M. Anderton to the Emerging Infectious Diseases (EID) Fellowship Program administered by the Association of Public Health Laboratories (APHL) and funded for by the CDC. Recombinant purified PsaA was provided by Sanofi Aventis, Toronto, Ont., Canada. We would like to thank E. Tuomanen (St. Jude Children's Hospital, Memphis, TN) for completing the pIgR experiments. Pnc PsaA − mutant was a gift from J. Paton (University of Adelaide, Australia). Lec5 and Neo cells were a gift from J. Stanley (University of Pennsylvania, Philadelphia, PA). We thank S. Hammerschmidt for helpful discussions, J. Gathany for photography (CDC, Atlanta, GA) and Y. Williamson (CDC, Atlanta, GA) and I. Gipson (Harvard University, Cambridge, MA) for providing conjunctival epithelial cells.
PY - 2007/5
Y1 - 2007/5
N2 - 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 α5 β1 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.
AB - 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 α5 β1 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.
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U2 - 10.1016/j.micpath.2007.02.003
DO - 10.1016/j.micpath.2007.02.003
M3 - Article
C2 - 17412553
AN - SCOPUS:34247485877
VL - 42
SP - 225
EP - 236
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
SN - 0882-4010
IS - 5-6
ER -