Capsular Polysaccharide Masks Clumping Factor A–Mediated Adherence of Staphylococcus aureus to Fibrinogen and Platelets
1Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; 2Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland
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.
Conclusion.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.
Received 16 November 2006; accepted 11 April 2007; electronically published 10 August 2007.
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Online publication date: 1-Sep-2008.
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Potential conflicts of interest: T.J.F. is a member of the scientific advisory board of Inhibitex, Inc., and holds the US patent on S. aureus clumping factor A. All other authors report no conflicts.
Presented in part: 104th General Meeting of the American Society for Microbiology, New Orleans, 23–27 May 2004 (abstract D‐254).
Financial support: National Institutes of Health (grants AI29040 and Fogarty Foundation TW006264 to J.C.L.); Science Foundation Ireland (grant 03/IN3/B370 to T.J.F.); Health Research Board of Ireland (grant RPO09/2002 to T.J.F.).