Capsular polysaccharide masks clumping factor A-mediated adherence of Staphylococcus aureus to fibrinogen and platelets.
BACKGROUND
Clumping factor A (ClfA) is a Staphylococcus aureus cell wall-associated adhesin that mediates staphylococcal binding to fibrinogen and platelets. Our goals were to determine whether expression of capsular polysaccharide (CP) affected ClfA-mediated adherence of S. aureus and to assess whether the length of the ClfA repeat region influenced this interaction.


METHODS
ClfA constructs with repeat regions of different lengths were introduced into isogenic S. aureus strains that expressed CP5, CP8, or no CP. S. aureus binding to fibrinogen was assessed in rabbit plasma and on fibrinogen-coated microtiter plates. Adherence of S. aureus strains to platelets was evaluated by flow cytometry and confocal microscopy.


RESULTS
As the length of the ClfA repeat region increased, binding of acapsular S. aureus to fibrinogen-coated microtiter plates was enhanced. By contrast, encapsulated S. aureus expressing the full-length ClfA were poorly adherent. The acapsular S. aureus mutant strain showed a 2-fold increase in platelet binding, compared with the isogenic encapsulated strains. By contrast, platelet aggregation was unaffected by CP production.


CONCLUSIONS
CP expression inhibits S. aureus ClfA-mediated binding to fibrinogen and platelets, and a full-length repeat region cannot overcome this inhibition. These findings have important implications for vaccine development, given that CP may mask surface adhesins.
Risley
Allison L
AL
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Loughman
Anthony
A
Cywes-Bentley
Colette
C
Foster
Timothy J
TJ
Lee
Jean C
JC
D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D016667:Bacterial Capsules / Q000737:chemistry*; D001792:Blood Platelets / Q000382:microbiology*; D003030:Coagulase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D013211:Staphylococcus aureus / Q000472:pathogenicity*
C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D011135:Polysaccharides, Bacterial; D005340:Fibrinogen