1887

Abstract

The interaction of bacteria with platelets is implicated in the pathogenesis of endovascular infections, including infective endocarditis, of which is the leading cause. Several surface proteins mediate aggregation of platelets by fibrinogen- or fibronectin-dependent processes, which also requires specific antibodies. In this study was grown in iron-limited medium to mimic conditions in which iron is unavailable to pathogens. Under such conditions, a mutant lacking the known platelet-activating surface proteins adhered directly to platelets in the absence of plasma proteins and triggered aggregation. Platelet adhesion and aggregation was prevented by inhibiting expression of iron-regulated surface determinant (Isd) proteins. Mutants defective in IsdB, but not IsdA or IsdH, were unable to adhere to or aggregate platelets. Antibodies to the platelet integrin GPIIb/IIIa inhibited platelet adhesion by IsdB-expressing strains, as did antagonists of GPIIb/IIIa. Surface plasmon resonance demonstrated that recombinant IsdB interacts directly with GPIIb/IIIa.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.036673-0
2010-03-01
2020-07-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/3/920.html?itemId=/content/journal/micro/10.1099/mic.0.036673-0&mimeType=html&fmt=ahah

References

  1. Calvete J. J.. 1999; Platelet integrin GPIIb/IIIa: structure-function correlations. An update and lessons from other integrins. Proc Soc Exp Biol Med222:29–38
    [Google Scholar]
  2. Clarke S. R., Wiltshire M. D., Foster S. J.. 2004; IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated adhesin. Mol Microbiol51:1509–1519
    [Google Scholar]
  3. Clarke S. R., Mohamed R., Bian L., Routh A. F., Kokai-Kun J. F., Mond J. J., Tarkowski A., Foster S. J.. 2007; The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe1:199–212
    [Google Scholar]
  4. Clarke S. R., Andre G., Walsh E. J., Dufrene Y. F., Foster T. J., Foster S. J.. 2009; Iron-regulated surface determinant protein A (IsdA) mediates adhesion of Staphylococcus aureus to human corneocyte envelope proteins. Infect Immun77:2408–2416
    [Google Scholar]
  5. Fitzgerald J. R., Foster T. J., Cox D.. 2006a; The interaction of bacterial pathogens with platelets. Nat Rev Microbiol4:445–457
    [Google Scholar]
  6. Fitzgerald J. R., Loughman A., Keane F., Brennan M., Knobel M., Higgins J., Visai L., Speziale P., Cox D., Foster T. J.. 2006b; Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the Fc γRIIa receptor. Mol Microbiol59:212–230
    [Google Scholar]
  7. Ford I., Douglas C. W., Heath J., Rees C., Preston F. E.. 1996; Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863. Br J Haematol94:729–739
    [Google Scholar]
  8. Grundmeier M., Hussain M., Becker P., Heilmann C., Peters G., Sinha B.. 2004; Truncation of fibronectin-binding proteins in Staphylococcus aureus strain Newman leads to deficient adherence and host cell invasion due to loss of the cell wall anchor function. Infect Immun72:7155–7163
    [Google Scholar]
  9. Hartford O. M., Wann E. R., Hook M., Foster T. J.. 2001; Identification of residues in the Staphylococcus aureus fibrinogen-binding MSCRAMM clumping factor A (ClfA) that are important for ligand binding. J Biol Chem276:2466–2473
    [Google Scholar]
  10. Kerrigan S. W., Douglas I., Wray A., Heath J., Byrne M. F., Fitzgerald D., Cox D.. 2002; A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation. Blood100:509–516
    [Google Scholar]
  11. Kerrigan S. W., Clarke N., Loughman A., Meade G., Foster T. J., Cox D.. 2008; Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro. Arterioscler Thromb Vasc Biol28:335–340
    [Google Scholar]
  12. Kuipers O. P., Beerthuyzen M. M., Siezen R. J., De Vos W. M.. 1993; Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis. Requirement of expression of the nisA and nisI genes for development of immunity. Eur J Biochem216:281–291
    [Google Scholar]
  13. Loughman A., Fitzgerald J. R., Brennan M. P., Higgins J., Downer R., Cox D., Foster T. J.. 2005; Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A. Mol Microbiol57:804–818
    [Google Scholar]
  14. Miajlovic H., Loughman A., Brennan M., Cox D., Foster T. J.. 2007; Both complement- and fibrinogen-dependent mechanisms contribute to platelet aggregation mediated by Staphylococcus aureus clumping factor B. Infect Immun75:3335–3343
    [Google Scholar]
  15. Moreillon P., Que Y. A.. 2004; Infective endocarditis. Lancet363:139–149
    [Google Scholar]
  16. Mylonakis E., Calderwood S. B.. 2001; Infective endocarditis in adults. N Engl J Med345:1318–1330
    [Google Scholar]
  17. O'Brien L., Kerrigan S. W., Kaw G., Hogan M., Penades J., Litt D., Fitzgerald D. J., Foster T. J., Cox D.. 2002; Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol44:1033–1044
    [Google Scholar]
  18. O'Connell D. P., Nanavaty T., McDevitt D., Gurusiddappa S., Hook M., Foster T. J.. 1998; The fibrinogen-binding MSCRAMM (clumping factor) of Staphylococcus aureus has a Ca2+-dependent inhibitory site. J Biol Chem273:6821–6829
    [Google Scholar]
  19. Pawar P., Shin P. K., Mousa S. A., Ross J. M., Konstantopoulos K.. 2004; Fluid shear regulates the kinetics and receptor specificity of Staphylococcus aureus binding to activated platelets. J Immunol173:1258–1265
    [Google Scholar]
  20. Petersen H. J., Keane C., Jenkinson H. F., Vickerman M. M., Jesionowski A., Waterhouse J. C., Cox D., Kerrigan S. W.. 2009; Human platelets recognize a novel surface protein PadA on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa. Infect Immun78:413–422
    [Google Scholar]
  21. Skaar E. P., Schneewind O.. 2004; Iron-regulated surface determinants (Isd) of Staphylococcus aureus: stealing iron from heme. Microbes Infect6:390–397
    [Google Scholar]
  22. Skaar E. P., Humayun M., Bae T., DeBord K. L., Schneewind O.. 2004; Iron-source preference of Staphylococcus aureus infections. Science305:1626–1628
    [Google Scholar]
  23. Visai L., Yanagisawa N., Josefsson E., Tarkowski A., Pezzali I., Rooijakkers S. H., Foster T. J., Speziale P.. 2009; Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH. Microbiology155:667–679
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.036673-0
Loading
/content/journal/micro/10.1099/mic.0.036673-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error