title: Flamingo cadherin: a putative host receptor for Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva, 84101, Israel.
authors.forename: Karin
authors.initials: K
authors.lastname: Blau
authors.forename: Maxim
authors.initials: M
authors.lastname: Portnoi
authors.forename: Marilou
authors.initials: M
authors.lastname: Shagan
authors.forename: Antonina
authors.initials: A
authors.lastname: Kaganovich
authors.forename: Slava
authors.initials: S
authors.lastname: Rom
authors.forename: Daniel
authors.initials: D
authors.lastname: Kafka
authors.forename: Vered
authors.initials: V
authors.lastname: Chalifa Caspi
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Noga
authors.initials: N
authors.lastname: Givon-Lavi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gershoni
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
authors.forename: Yaffa
authors.initials: Y
authors.lastname: Mizrachi Nebenzahl
mesh_terms: D018829:Adhesins, Bacterial / Q000302:isolation & purification* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology*; D015820:Cadherins / Q000302:isolation & purification / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000517:prevention & control; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D053585:Virus Attachment
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; C454220:CELSR1 cadherin, human; D015820:Cadherins; D011994:Recombinant Proteins; D005634:Fructose-Bisphosphate Aldolase