TY - JOUR
T1 - Flamingo cadherin
T2 - A putative host receptor for Streptococcus pneumoniae
AU - Blau, Karin
AU - Portnoi, Maxim
AU - Shagan, Marilou
AU - Kaganovich, Antonina
AU - Rom, Slava
AU - Kafka, Daniel
AU - Caspi, Vered Chalifa
AU - Porgador, Angel
AU - Givon-Lavi, Noga
AU - Gershoni, Jonathan M.
AU - Dagan, Ron
AU - Nebenzahl, Yaffa Mizrachi
N1 - Funding Information:
Received 10 September 2006; accepted 2 January 2007; electronically published 3 May 2007. Potential conflicts of interest: none reported. Presented in part: 5th International Symposium on Pneumococci and Pneumococcal Diseases, Alice Springs, Australia, 2–6 April 2006 (presentation SY8.04). Financial support: Israeli Ministry of Health (grants 4476 and 5540); BGNegev Biotechnology; Ben Gurion University Seed Money (grant 80904101 to Y.M.N.); Center of Emerging Diseases (grant 2506 to Y.M.N.); Israel Academy of Science (grant 613/04 to Y.M.N.). a K.B. and M.P. contributed equally to the article. Reprints or correspondence: Prof. Yaffa Mizrachi Nebenzahl, Pediatric Infectious Disease Unit, Soroka University Medical Center, Dept. of Microbiology and Immunology, 4101, PO Box 151, Beer Sheva 84101, Israel ([email protected]).
PY - 2007/6/15
Y1 - 2007/6/15
N2 - Streptococcus pneumoniae fructose bisphosphate aldolase (FBA) is a cell wall-localized lectin. We demonstrate that recombinant (r) FBA and anti-rFBA antibodies inhibit encapsulated and unencapsulated S. pneumoniae serotype 3 adherence to A549 type II lung carcinoma epithelial cells. A random combinatorial peptide library expressed by filamentous phage was screened with rFBA. Eleven of 30 rFBA-binding phages inhibited 90% of S. pneumoniae adhesion to A549 cells. The insert peptide sequence of 9 of these phages matched the Flamingo cadherin receptor (FCR) when aligned against the human genome. A peptide comprising a putative FBA-binding region of FCR (FCRP) inhibited 2 genetically and capsularly unrelated pairs of encapsulated and unencapsulated S. pneumoniae strains from binding to A549 cells. Moreover, FCRP inhibited S. pneumoniae nasopharyngeal and lung colonization and, possibly, pneumonia development in the mouse intranasal inoculation model system. These data indicate that FBA is an S. pneumoniae adhesin and that FCR is its host receptor.
AB - Streptococcus pneumoniae fructose bisphosphate aldolase (FBA) is a cell wall-localized lectin. We demonstrate that recombinant (r) FBA and anti-rFBA antibodies inhibit encapsulated and unencapsulated S. pneumoniae serotype 3 adherence to A549 type II lung carcinoma epithelial cells. A random combinatorial peptide library expressed by filamentous phage was screened with rFBA. Eleven of 30 rFBA-binding phages inhibited 90% of S. pneumoniae adhesion to A549 cells. The insert peptide sequence of 9 of these phages matched the Flamingo cadherin receptor (FCR) when aligned against the human genome. A peptide comprising a putative FBA-binding region of FCR (FCRP) inhibited 2 genetically and capsularly unrelated pairs of encapsulated and unencapsulated S. pneumoniae strains from binding to A549 cells. Moreover, FCRP inhibited S. pneumoniae nasopharyngeal and lung colonization and, possibly, pneumonia development in the mouse intranasal inoculation model system. These data indicate that FBA is an S. pneumoniae adhesin and that FCR is its host receptor.
UR - http://www.scopus.com/inward/record.url?scp=34249908935&partnerID=8YFLogxK
U2 - 10.1086/518038
DO - 10.1086/518038
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AN - SCOPUS:34249908935
SN - 0022-1899
VL - 195
SP - 1828
EP - 1837
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -
