Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor.
The Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. Although the invasive disease is severe, some 40% of individuals harbour the pneumococcus in the nasopharynx asymptomatically. Here we investigate the molecular elements of the encounter between host and pathogen that distinguish these different outcomes. We show that inflammatory activation of human cells shifts the targeting of the pneumococcus to a new receptor, that for the G-protein-coupled platelet-activating factor (PAF). Only virulent pneumococci engage the PAF receptor. Attachment of the bacterial phosphorylcholine to the PAF receptor enhanced adherence, which was coupled to invasion of endothelial, epithelial and PAF-receptor-transfected cells. This progression could be arrested in vitro and in vivo by PAF-receptor-specific antagonists, suggesting a possible approach to therapy.
Cundell
D R
DR
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021-6399, USA.
Gerard
N P
NP
Gerard
C
C
Idanpaan-Heikkila
I
I
Tuomanen
E I
EI
D001422:Bacterial Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000382:microbiology*; D005663:Furans / Q000494:pharmacology; D006801:Humans; D010767:Phosphorylcholine / Q000378:metabolism; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013296:Streptococcus pneumoniae / Q000472:pathogenicity / Q000502:physiology*; D014162:Transfection; D014774:Virulence
D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D010767:Phosphorylcholine; C054893:L 659989