Article

Capsular polysaccharide masks clumping factor A-mediated adherence of Staphylococcus aureus to fibrinogen and platelets.

Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
The Journal of Infectious Diseases (impact factor: 6.41). 10/2007; 196(6):919-27. DOI:10.1086/520932 pp.919-27
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

acapsular S. aureus
 
acapsular S. aureus mutant strain
 
ClfA repeat region
 
confocal microscopy
 
CP expression inhibits S. aureus ClfA-mediated binding
 
different lengths
 
encapsulated S. aureus
 
fibrinogen-coated microtiter plates
 
flow cytometry
 
full-length ClfA
 
full-length repeat region
 
isogenic encapsulated strains
 
isogenic S. aureus strains
 
mediates staphylococcal binding
 
platelet aggregation
 
platelet binding
 
S. aureus
 
S. aureus binding
 
S. aureus strains
 
vaccine development