Flamingo cadherin: a putative host receptor for Streptococcus pneumoniae.
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.
Blau
Karin
K
Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva, 84101, Israel.
Portnoi
Maxim
M
Shagan
Marilou
M
Kaganovich
Antonina
A
Rom
Slava
S
Kafka
Daniel
D
Chalifa Caspi
Vered
V
Porgador
Angel
A
Givon-Lavi
Noga
N
Gershoni
Jonathan M
JM
Dagan
Ron
R
Mizrachi Nebenzahl
Yaffa
Y
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
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; C454220:CELSR1 cadherin, human; D015820:Cadherins; D011994:Recombinant Proteins; D005634:Fructose-Bisphosphate Aldolase