Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The interaction of bacterial pathogens with platelets

Key Points

  • The interaction of bacteria with platelets is important in the pathogenesis of endovascular infections and probably in some cardiovascular diseases.

  • When bacteria interact with platelets, intracellular signalling pathways are stimulated. This results in activation of platelets and subsequently in aggregation.

  • Two groups of bacteria (Staphylococcus aureus and the oral streptococci S. sanguis and S. gordonii) are responsible for the majority of cases of infective endocarditis. The bacterial surface proteins involved in binding receptors on the surface of resting platelets have been identified.

  • In some cases, activation is triggered by platelets binding to complement components that have been deposited on bacterial cells during complement fixation.

  • The platelet receptor for IgG (FcγRIIa) is of central importance. Many bacterial interactions with platelets trigger activation and aggregation.

Abstract

In recent years, the frequency of serious cardiovascular infections such as endocarditis has increased, particularly in association with nosocomially acquired antibiotic-resistant pathogens. Growing evidence suggests a crucial role for the interaction of bacteria with human platelets in the pathogenesis of cardiovascular infections. Here, we review the nature of the interactions between platelets and bacteria, and the role of these interactions in the pathogenesis of endocarditis and other cardiovascular diseases.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Platelet activation and aggregation.
Figure 2: Signalling pathways in platelet activation.
Figure 3: The mechanism of Staphylococcus aureus-mediated platelet adherence and activation.
Figure 4: Bacterial interactions involving the platelet glycoprotein GPIb.
Figure 5: Platelet interactions of the staphylococcal secreted proteins Efb and α-toxin.

Similar content being viewed by others

References

  1. Petti, C. A. & Fowler, V. G. Jr. Staphylococcus aureus bacteremia and endocarditis. Cardiol. Clin. 21, 219?233 (2003).

    Article  PubMed  Google Scholar 

  2. Levi, M., Keller, T. T., van Gorp, E. & ten Cate, H. Infection and inflammation and the coagulation system. Cardiovasc. Res. 60, 26?39 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Franchini, M. & Veneri, D. Helicobacter pylori infection and immune thrombocytopenic purpura: an update. Helicobacter 9, 342?346 (2004).

    Article  PubMed  Google Scholar 

  4. Ishani, A., Collins, A. J., Herzog, C. A. & Foley, R. N. Septicemia, access and cardiovascular disease in dialysis patients: The USRDS wave 2 study. Kid ney Int. 68, 311 (2005).

    Article  Google Scholar 

  5. Foley, R. N., Guo, H., Snyder, J. J., Gilbertson, D. T. & Collins, A. J. Septicemia in the United States dialysis population, 1991 to 1999. J. Am. Soc. Nephrol. 15, 1038?1045 (2004).

    Article  PubMed  Google Scholar 

  6. Corrado, E. et al. Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study. Stroke 37, 482?486 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Kerrigan, S. W. et al. A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation. Blood 100, 509?516 (2002). Demonstrates the role of GPIb in S. sanguis -mediated platelet aggregation.

    Article  CAS  PubMed  Google Scholar 

  8. O'Brien, L. et al. 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. Microbiol. 44, 1033?1044 (2002). Identifies ClfA as a key mediator of S. aureus -induced aggregation.

    Article  CAS  PubMed  Google Scholar 

  9. Bhakdi, S. et al. Staphylococcal α-toxin promotes blood coagulation via attack on human platelets. J. Exp. Med. 168, 527?542 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Born, G. The aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194, 927?929 (1962).

    Article  CAS  PubMed  Google Scholar 

  11. Emilia, G. et al. Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura. Blood 97, 812?814 (2001). Shows an association between H. pylori infection and thrombocytopenia.

    Article  CAS  PubMed  Google Scholar 

  12. Veneri, D., Krampera, M. & Franchini, M. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study. Platelets 16, 117?119 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Guessous, F. et al. Shiga toxin 2 and lipopolysaccharide cause monocytic THP-1 cells to release factors which activate platelet function. Thromb. Haemost. 94, 1019?1027 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Hambleton, J., Leung, L. L. & Levi, M. Coagulation: consultative hemostasis. Hematology 2002, 335?352 (2002).

    Article  Google Scholar 

  15. Proulx, F., Seidman, E. G. & Karpman, D. Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome. Pediatr. Res. 50, 163?171 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Schierholz, J., Beuth, J. & Pulverer, G. ?Difficult to treat infections? pharmacokinetic and pharmacodynamic factors?a review. Acta Microbiol. Immunol. Hung. 47, 1?8 (2000).

    CAS  PubMed  Google Scholar 

  17. Yeaman, M. & Bayer, A. Antimicrobial host defense. In Platelets (ed. Michelson, A. D.) 469?490 (Academic Press, London, 2002).

    Google Scholar 

  18. Wisplinghoff, H. et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39, 309?317 (2004).

    Article  PubMed  Google Scholar 

  19. Petti, C. A. & Fowler, V. G. Jr. Staphylococcus aureus bacteremia and endocarditis. Infect. Dis. Clin. North Am. 16, 413?435, x?xi (2002).

    Article  PubMed  Google Scholar 

  20. Lowy, F. D. Antimicrobial resistance: the example of Staphylococcus aureus. J. Clin. Invest. 111, 1265?1273 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Muhlestein, J. B. & Anderson, J. L. Chronic infection and coronary artery disease. Cardiol. Clin. 21, 333?362 (2003).

    Article  PubMed  Google Scholar 

  22. Ott, S. J. et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation 113, 929?937 (2006). Shows the presence of many pathogens in atherosclerotic plaques.

    Article  PubMed  Google Scholar 

  23. Zhu, J. et al. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation 103, 45?51 (2001). Suggests that the number of different infections that a patient has had is a predictor of cardiovascular outcome.

    Article  CAS  PubMed  Google Scholar 

  24. Elkind, M. & Cole, J. Do common infections cause stroke? Semin. Neurol. 26, 88?99 (2006).

    Article  PubMed  Google Scholar 

  25. Baddour, L. M. et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111, e394?e434 (2005). Important guideline document on infective endocarditis from the American Heart Association.

    Article  PubMed  Google Scholar 

  26. Moreillon, P. & Que, Y. A. Infective endocarditis. Lancet 363, 139?149 (2004).

    Article  PubMed  Google Scholar 

  27. Fowler, V. G. Jr et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 293, 3012?3021 (2005). Shows that S. aureus is now the most common cause of IE in the developed world.

    Article  CAS  PubMed  Google Scholar 

  28. Seymour, R. A., Preshaw, P. M., Thomason, J. M., Ellis, J. S. & Steele, J. G. Cardiovascular diseases and periodontology. J. Clin. Periodontol. 30, 279?292 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Gupta, S. et al. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 96, 404?407 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Gurfinkel, E., Bozovich, G., Daroca, A., Beck, E. & Mautner, B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 350, 404 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Meier, C. R., Derby, L. E., Jick, S. S., Vasilakis, C. & Jick, H. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA 281, 427?431 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. Jespersen, C. M. et al. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ 332, 22?27 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Andraws, R., Berger, J. & Brown, D. Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials. JAMA 293, 2641?2647 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Espinola-Klein, C. et al. Impact of infectious burden on extent and long-term prognosis of atherosclerosis. Circulation 105, 15?21 (2002).

    Article  PubMed  Google Scholar 

  35. Rupprecht, H. J. et al. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation 104, 25?31 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Brodala, N. et al. Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis in normocholesterolemic and hypercholesterolemic pigs. Arterioscler. Thromb. Vasc. Biol. 25, 1446?1451 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Lalla, E. et al. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler. Thromb. Vasc. Biol. 23, 1405?1411 (2003). Shows that normal exposure to an oral pathogen enhances atherosclerosis without bacteraemia.

    Article  CAS  PubMed  Google Scholar 

  38. Li, L., Messas, E., Batista, E. L. Jr, Levine, R. A. & Amar, S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation 105, 861?867 (2002). Shows that exposure to bacteria enhances atherosclerosis in a mouse model.

    Article  PubMed  Google Scholar 

  39. Gawaz, M. Platelets in the onset of atherosclerosis. Blood Cells Mol. Dis. 36, 206?210 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Shoji, T. et al. Platelet-monocyte aggregates are independently associated with occurrence of carotid plaques in type 2 diabetic patients. J. Atheroscler. Thromb. 12, 344?352 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Shoji, T. et al. Platelet activation is associated with hypoadiponectinemia and carotid atherosclerosis. Atherosclerosis 28 Nov 2005 (doi:10.1016/j.atherosclerosis.2005.10.034).

  42. Hartwig, J. H. Platelet structure. In Platelets (ed. Michelson, A. D.) 37?52 (Academic Press, London. 2002).

    Google Scholar 

  43. Macaulay, I. C. et al. Platelet genomics and proteomics in human health and disease. J. Clin. Invest. 115, 3370?3377 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Reed, G. Platelet secretion. In Platelets (ed. Michelson, A. D.) 181?196 (Academic Press, London, 2002).

    Google Scholar 

  45. Furie, B. & Furie, B. C. Thrombus formation in vivo. J. Clin. Invest. 115, 3355?3362 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shattil, S. J. & Newman, P. J. Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 104, 1606?1615 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Yeaman, M. R. & Bayer, A. S. Antimicrobial peptides from platelets. Drug. Resist. Updat. 2, 116?126 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Yeaman, M. R., Tang, Y. Q., Shen, A. J., Bayer, A. S. & Selsted, M. E. Purification and in vitro activities of rabbit platelet microbicidal proteins. Infect. Immun. 65, 1023?1031 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yeaman, M. R. The role of platelets in antimicrobial host defense. Clin. Infect. Dis. 25, 951?968 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Cole, A. M. et al. Cutting edge: IFN-inducible ELR-CXC chemokines display defensin-like antimicrobial activity. J. Immunol. 167, 623?627 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Krijgsveld, J. et al. Thrombocidins, microbicidal proteins from human blood platelets, are C-terminal deletion products of CXC chemokines. J. Biol. Chem. 275, 20374?20381 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Tang, Y. Q., Yeaman, M. R. & Selsted, M. E. Antimicrobial peptides from human platelets. Infect. Immun. 70, 6524?6533 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bayer, A. S. et al. In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source. Antimicrob. Agents Chemother. 42, 3169?3172 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fowler, V. G. et al. In vitro resistance to thrombin-induced platelet microbicidal protein in isolates of Staphylococcus aureus from endocarditis patients correlates with an intravascular device source. J. Infect. Dis. 182, 1251?1254 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Fowler, V. G. et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J. Infect. Dis. 190, 1140?1149 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Dhawan, V. K. et al. Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus. Infect. Immun. 65, 3293?3299 (1997). Suggests that strains which are more resistant to PMPs might also be more virulent.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bayer, A. S. et al. In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity. Infect. Immun. 68, 3548?3553 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bayer, A. S. et al. Transposon disruption of the complex I NADH oxidoreductase gene (snoD) in Staphylococcus aureus is associated with reduced susceptibility to the microbicidal activity of thrombin-induced platelet microbicidal protein 1. J. Bacteriol. 188, 211?222 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Koo, S. P., Bayer, A. S., Kagan, B. L. & Yeaman, M. R. Membrane permeabilization by thrombin-induced platelet microbicidal protein 1 is modulated by transmembrane voltage polarity and magnitude. Infect. Immun. 67, 2475?2481 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Weidenmaier, C. et al. DltABCD- and MprF-mediated cell envelope modifications of Staphylococcus aureus confer resistance to platelet microbicidal proteins and contribute to virulence in a rabbit endocarditis model. Infect. Immun. 73, 8033?8038 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kupferwasser, L. I. et al. Plasmid-mediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: role of the qacA locus. Antimicrob. Agents Chemother. 43, 2395?2399 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Pawar, P., Shin, P. K., Mousa, S. A., Ross, J. M. & Konstantopoulos, K. Fluid shear regulates the kinetics and receptor specificity of Staphylococcus aureus binding to activated platelets. J. Immunol. 173, 1258?1265 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Youssefian, T., Drouin, A., Masse, J. M., Guichard, J. & Cramer, E. M. Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 99, 4021?4029 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Rooijakkers, S. H., van Kessel, K. P. & van Strijp, J. A. Staphylococcal innate immune evasion. Trends Microbiol. 13, 596?601 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Foster, T. J. Immune evasion by staphylococci. Nature Rev. Microbiol. 3, 948?958 (2005).

    Article  CAS  Google Scholar 

  66. Levin, J. The evolution of mammalian platelets. In Platelets (ed. Michelson, A. D.) 3?20 (Academic Press, London, 2002).

    Google Scholar 

  67. Des Prez, R., Horowitz, H. I. & Hook, E. W. Effects of bacterial endotoxin on rabbit platelets: I. Platelet aggregation and release of platelet factors in vitro. J. Exp. Med. 114, 857?874 (1961).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Copley, A., Maupin, B. & Balea, T. The agglutinant and adhesive behaviour of isolated human and rabbit platelets in contact with various strains of mycobacteria. Acta Tuberc. Scand. 37, 151?161 (1959).

    CAS  PubMed  Google Scholar 

  69. Clawson, C. Platelet interaction with bacteria. III. Ultrastructure. Am. J. Pathol. 70, 449?471 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Clawson, C., Rao, G. & White, J. G. Platelet interaction with bacteria. IV. Stimulation of the release reaction. Am. J. Pathol. 81, 411?420 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Clawson, C. & White, J. G. Platelet interaction with bacteria. V. Ultrastructure of congenital afibrinogenemic platelets. Am. J. Pathol. 98, 197?211 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Clawson, C., White, J. G. & Herzberg, M. Platelet interaction with bacteria. VI. Contrasting the role of fibrinogen and fibronectin. Am. J. Hematol. 9, 45?53 (1980).

    Article  Google Scholar 

  73. Clawson, C. & White, J. G. Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors. Am. J. Pathol. 65, 367?380 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Clawson, C. & White, J. G. Platelet interaction with bacteria. II. Fate of the bacteria. Am. J. Pathol. 65, 381?397 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Humphrey, J. H. & Jaques, R. The release of histamine and 5-hydroxytryptamine (serotonin) from platelets by antigen?antibody reactions (in vitro). J. Physiol. 128, 9 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hawiger, J., Marney, S. R. Jr, Colley, D. G. & Des Prez, R. M. Complement-dependent platelet injury by staphylococcal protein A. J. Exp. Med. 136, 68?80 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Weksler, B. B. & Nachman, R. Rabbit platelet bactericidal protein. J. Exp. Med. 134, 1114?1130 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Manohar, M., Maheswaran, S. K., Frommes, S. P. & Lindorfer, R. K. Platelet damaging factor, a fifth activity of staphylococcal α-toxin. J. Bacteriol. 94, 224?231 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hawiger, J. et al. Staphylococci-induced human platelet injury mediated by protein A and immunoglobulin G Fc fragment receptor. J. Clin. Invest. 64, 931?937 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Moreillon, P. et al. Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis. Infect. Immun. 63, 4738?4743 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bayer, A. S. et al. Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent mechanism which is independent of principal platelet glycoprotein IIb/IIIa fibrinogen-binding domains. Infect. Immun. 63, 3634?3641 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Foster, T. J. & Hook, M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol. 6, 484?488 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Schwarz-Linek, U. et al. Pathogenic bacteria attach to human fibronectin through a tandem β-zipper. Nature 423, 177?181 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Massey, R. C. et al. Fibronectin-binding protein A of Staphylococcus aureus has multiple, substituting, binding regions that mediate adherence to fibronectin and invasion of endothelial cells. Cell. Microbiol. 3, 839?851 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Herrmann, M., Lai, Q. J., Albrecht, R. M., Mosher, D. F. & Proctor, R. A. Adhesion of Staphylococcus aureus to surface-bound platelets: role of fibrinogen/fibrin and platelet integrins. J. Infect. Dis. 167, 312?322 (1993).

    Article  CAS  PubMed  Google Scholar 

  86. Sullam, P. M., Bayer, A. S., Foss, W. M. & Cheung, A. L. Diminished platelet binding in vitro by Staphylococcus aureus is associated with reduced virulence in a rabbit model of infective endocarditis. Infect. Immun. 64, 4915?4921 (1996). Suggests a key role for bacteria?platelet interactions in IE pathogenesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Siboo, I. R., Cheung, A. L., Bayer, A. S. & Sullam, P. M. Clumping factor A mediates binding of Staphylococcus aureus to human platelets. Infect. Immun. 69, 3120?3127 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Loughman, A. et al. Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A. Mol. Microbiol. 57, 804?818 (2005). Shows the role for antibody and complement in ClfA-mediated aggregation.

    Article  CAS  PubMed  Google Scholar 

  89. Fitzgerald, J. R. et al. 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 FcγRIIa receptor. Mol. Microbiol. 59, 212?230 (2006). Describes the molecular mechanisms of FnBP-mediated platelet aggregation.

    Article  CAS  PubMed  Google Scholar 

  90. Saravia-Otten, P., Muller, H. P. & Arvidson, S. Transcription of Staphylococcus aureus fibronectin binding protein genes is negatively regulated by agr and an agr-independent mechanism. J. Bacteriol. 179, 5259?5263 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Que, Y. A. et al. Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis. J. Exp. Med. 201, 1627?1635 (2005). Animal data on the roles of ClfA and FnBp in IE.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Casolini, F. et al. Antibody response to fibronectin-binding adhesin FnbpA in patients with Staphylococcus aureus infections. Infect. Immun. 66, 5433?5442 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Heilmann, C. et al. Staphylococcus aureus fibronectin-binding protein (FnBP)-mediated adherence to platelets, and aggregation of platelets induced by FnBPA but not by FnBPB. J. Infect. Dis. 190, 321?329 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Niemann, S. et al. Soluble fibrin is the main mediator of Staphylococcus aureus adhesion to platelets. Circulation 110, 193?200 (2004).

    Article  CAS  PubMed  Google Scholar 

  95. Dryla, A. et al. Comparison of antibody repertoires against Staphylococcus aureus in healthy individuals and in acutely infected patients. Clin. Diagn. Lab. Immunol. 12, 387?398 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Nguyen, T., Ghebrehiwet, B. & Peerschke, E. I. Staphylococcus aureus protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcal interactions with platelets. Infect. Immun. 68, 2061?2068 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hartleib, J. et al. Protein A is the von Willebrand factor binding protein on Staphylococcus aureus. Blood 96, 2149?2156 (2000).

    CAS  PubMed  Google Scholar 

  98. Siboo, I. R., Chambers, H. F. & Sullam, P. M. Role of SraP, a serine-rich surface protein of Staphylococcus aureus, in binding to human platelets. Infect. Immun. 73, 2273?2280 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ford, I., Douglas, C. W., Heath, J., Rees, C. & Preston, F. E. Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863. Br. J. Haematol. 94, 729?739 (1996). Identifies a role for complement in S. sanguis -induced platelet aggregation.

    Article  CAS  PubMed  Google Scholar 

  100. Herzberg, M. C. et al. The platelet interactivity phenotype of Streptococcus sanguis influences the course of experimental endocarditis. Infect. Immun. 60, 4809?4818 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Beachey, E. H. & Stollerman, G. H. Toxic effects of streptococcal M protein on platelets and polymorphonuclear leukocytes in human blood. J. Exp. Med. 134, 351?365 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kurpiewski, G. E., Forrester, L. J., Campbell, B. J. & Barrett, J. T. Platelet aggregation by Streptococcus pyogenes. Infect. Immun. 39, 704?708 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Herzberg, M. C., Brintzenhofe, K. L. & Clawson, C. C. Aggregation of human platelets and adhesion of Streptococcus sanguis. Infect. Immun. 39, 1457?1469 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Erickson, P. R. & Herzberg, M. C. A collagen-like immunodeterminant on the surface of Streptococcus sanguis induces platelet aggregation. J. Immunol. 138, 3360?3366 (1987).

    CAS  PubMed  Google Scholar 

  105. Erickson, P. R. & Herzberg, M. C. The Streptococcus sanguis platelet aggregation-associated protein. Identification and characterization of the minimal platelet-interactive domain. J. Biol. Chem. 268, 1646?1649 (1993).

    Article  CAS  PubMed  Google Scholar 

  106. Gong, K., Wen, D. Y., Ouyang, T., Rao, A. T. & Herzberg, M. C. Platelet receptors for the Streptococcus sanguis adhesin and aggregation-associated antigens are distinguished by anti-idiotypical monoclonal antibodies. Infect. Immun. 63, 3628?3633 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Herzberg, M. C. et al. Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis. J. Periodontol. 76, 2101?2105 (2005).

    Article  PubMed  Google Scholar 

  108. Sullam, P. M., Jarvis, G. A. & Valone, F. H. Role of immunoglobulin G in platelet aggregation by viridans group streptococci. Infect. Immun. 56, 2907?2911 (1988). Early paper showing a role for IgG in streptococci-induced platelet aggregation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. McNicol, A. et al. A role for immunoglobulin G in donor-specific Streptococcus sanguis-induced platelet aggregation. Thromb. Haemost. 95, 288?293 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Ford, I. et al. The role of immunoglobulin G and fibrinogen in platelet aggregation by Streptococcus sanguis. Br. J. Haematol. 97, 737?746 (1997).

    Article  CAS  PubMed  Google Scholar 

  111. Ford, I., Douglas, C. W., Preston, F. E., Lawless, A. & Hampton, K. K. Mechanisms of platelet aggregation by Streptococcus sanguis, a causative organism in infective endocarditis. Br. J. Haematol. 84, 95?100 (1993).

    Article  CAS  PubMed  Google Scholar 

  112. Plummer, C. et al. A serine-rich glycoprotein of Streptococcus sanguis mediates adhesion to platelets via GPIb. Br. J. Haematol. 129, 101?109 (2005). Identifies SrpA as the S. sanguis protein that interacts with GPIb.

    Article  CAS  PubMed  Google Scholar 

  113. Sullam, P. M., Valone, F. H. & Mills, J. Mechanisms of platelet aggregation by viridans group streptococci. Infect. Immun. 55, 1743?1750 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Pampolina, C. & McNicol, A. Streptococcus sanguis-induced platelet activation involves two waves of tyrosine phosphorylation mediated by FcgRIIA and aIIbb3. Thromb. Haemost. 93, 932?939 (2005).

    Article  CAS  PubMed  Google Scholar 

  115. Sullam, P. M. et al. Physical proximity and functional interplay of the glycoprotein Ib-IX-V-complex and the Fc receptor Fcγ RIIA on the platelet plasma membrane. J. Biol. Chem. 273, 5331?5336 (1998). Identifies an association between GPIb and Fc γ RIIa on the platelet surface.

    Article  CAS  PubMed  Google Scholar 

  116. Douglas, C. W., Heath, J., Hampton, K. K. & Preston, F. E. Identity of viridans streptococci isolated from cases of infective endocarditis. J. Med. Microbiol. 39, 179?182 (1993).

    Article  CAS  PubMed  Google Scholar 

  117. Douglas, C. W., Brown, P. R. & Preston, F. E. Platelet aggregation by oral streptococci. FEMS Microbiol. Lett. 60, 63?67 (1990).

    Article  CAS  PubMed  Google Scholar 

  118. Bensing, B. A., Gibson, B. W. & Sullam, P. M. The Streptococcus gordonii platelet binding protein GspB undergoes glycosylation independently of export. J. Bacteriol. 186, 638?645 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bensing, B. A., Lopez, J. A. & Sullam, P. M. The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibα. Infect. Immun. 72, 6528?6537 (2004). Identifies S. gordonii proteins that interact with GPIb.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Takahashi, Y., Yajima, A., Cisar, J. O. & Konishi, K. Functional analysis of the Streptococcus gordonii DL1 sialic acid-binding adhesin and its essential role in bacterial binding to platelets. Infect. Immun. 72, 3876?3882 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bensing, B. A. & Sullam, P. M. An accessory sec locus of Streptococcus gordonii is required for export of the surface protein GspB and for normal levels of binding to human platelets. Mol. Microbiol. 44, 1081?1094 (2002).

    Article  CAS  PubMed  Google Scholar 

  122. Takamatsu, D., Bensing, B. A. & Sullam, P. M. Genes in the accessory sec locus of Streptococcus gordonii have three functionally distinct effects on the expression of the platelet-binding protein GspB. Mol. Microbiol. 52, 189?203 (2004).

    Article  CAS  PubMed  Google Scholar 

  123. Takamatsu, D., Bensing, B. A. & Sullam, P. M. Four proteins encoded in the gspB-secY2A2 operon of Streptococcus gordonii mediate the intracellular glycosylation of the platelet-binding protein GspB. J. Bacteriol. 186, 7100?7111 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Yajima, A., Takahashi, Y. & Konishi, K. Identification of platelet receptors for the Streptococcus gordonii DL1 sialic acid-binding adhesin. Microbiol. Immunol. 49, 795?800 (2005).

    Article  CAS  PubMed  Google Scholar 

  125. Takamatsu, D. et al. Binding of the Streptococcus gordonii surface glycoproteins GspB and Hsa to specific carbohydrate structures on platelet membrane glycoprotein Ibα. Mol. Microbiol. 58, 380?392 (2005).

    Article  CAS  PubMed  Google Scholar 

  126. Jakubovics, N. S. et al. Functions of cell surface-anchored antigen I/II family and Hsa polypeptides in interactions of Streptococcus gordonii with host receptors. Infect. Immun. 73, 6629?6638 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Takamatsu, D., Bensing, B. A., Prakobphol, A., Fisher, S. J. & Sullam, P. M. Binding of the streptococcal surface glycoproteins GspB and Hsa to human salivary proteins. Infect. Immun. 74, 1933?1940 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Takahashi, Y. et al. Contribution of sialic acid-binding adhesin to pathogenesis of experimental endocarditis caused by Streptococcus gordonii DL1. Infect. Immun. 74, 740?743 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Bensing, B. A., Rubens, C. E. & Sullam, P. M. Genetic loci of Streptococcus mitis that mediate binding to human platelets. Infect. Immun. 69, 1373?1380 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rasmussen, M., Eden, A. & Bjorck, L. SclA, a novel collagen-like surface protein of Streptococcus pyogenes. Infect. Immun. 68, 6370?6377 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Zimmerman, T. S. & Spiegelberg, H. L. Pneumococcus-induced serotonin release from human platelets. Identification of the participating plasma/serum factor as immunoglobulin. J. Clin. Invest. 56, 828?834 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Pietrocola, G. et al. FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation. Blood 105, 1052?1059 (2005).

    Article  CAS  PubMed  Google Scholar 

  133. Sjobring, U., Ringdahl, U. & Ruggeri, Z. M. Induction of platelet thrombi by bacteria and antibodies. Blood 100, 4470?4477 (2002). Describes the interaction of bacteria and platelets under physiological shear conditions.

    Article  CAS  PubMed  Google Scholar 

  134. Curtis, M. A., Macey, M., Slaney, J. M. & Howells, G. L. Platelet activation by Protease I of Porphyromonas gingivalis W83. FEMS Microbiol. Lett. 110, 167?173 (1993).

    Article  CAS  PubMed  Google Scholar 

  135. Naito, M. et al. Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase. Mol. Microbiol. 59, 152?167 (2006).

    Article  CAS  PubMed  Google Scholar 

  136. Blaser, M. J. & Atherton, J. C. Helicobacter pylori persistence: biology and disease. J. Clin. Invest. 113, 321?333 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Danesh, J. et al. Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. BMJ 319, 1157?1162 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Pellicano, R., Fagoonee, S., Rizzetto, M. & Ponzetto, A. Helicobacter pylori and coronary heart disease: which directions for future studies? Crit. Rev. Microbiol. 29, 351?359 (2003).

    Article  PubMed  Google Scholar 

  139. Byrne, M. F. et al. Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation. Gastroenterology 124, 1846?1854 (2003).

    Article  CAS  PubMed  Google Scholar 

  140. Morton, A. R. et al. Campylobacter induced thrombotic thrombocytopenic purpura. Lancet 326, 1133?1134 (1985).

    Article  Google Scholar 

  141. Sharma, A. et al. Porphyromonas gingivalis platelet aggregation activity: outer membrane vesicles are potent activators of murine platelets. Oral Microbiol. Immunol. 15, 393?396 (2000).

    Article  CAS  PubMed  Google Scholar 

  142. Stanek, G. & Strle, F. Lyme borreliosis. Lancet 362, 1639?1647 (2003).

    Article  PubMed  Google Scholar 

  143. Coburn, J., Leong, J. M. & Erban, J. K. Integrin αIIbβ3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. Proc. Natl Acad. Sci. USA 90, 7059?7063 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Defoe, G. & Coburn, J. Delineation of Borrelia burgdorferi p66 sequences required for integrin α(IIb)β(3) recognition. Infect. Immun. 69, 3455?3459 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Perine, P. L., Parry, E. H., Vukotich, D., Warrell, D. A. & Bryceson, A. D. Bleeding in louse-borne relapsing fever. I. Clinical studies in 37 patients. Trans. R. Soc. Trop. Med. Hyg. 65, 776?781 (1971).

    Article  CAS  PubMed  Google Scholar 

  146. Alugupalli, K. R. et al. Platelet activation by a relapsing fever spirochaete results in enhanced bacterium?platelet interaction via integrin αIIbβ3 activation. Mol. Microbiol. 39, 330?340 (2001).

    Article  CAS  PubMed  Google Scholar 

  147. Alugupalli, K. R. et al. Spirochete?platelet attachment and thrombocytopenia in murine relapsing fever borreliosis. Blood 102, 2843?2850 (2003).

    Article  CAS  PubMed  Google Scholar 

  148. Arvand, M., Bhakdi, S., Dahlback, B. & Preissner, K. T. Staphylococcus aureus α-toxin attack on human platelets promotes assembly of the prothrombinase complex. J. Biol. Chem. 265, 14377?14381 (1990).

    Article  CAS  PubMed  Google Scholar 

  149. Bayer, A. S. et al. Hyperproduction of α-toxin by Staphylococcus aureus results in paradoxically reduced virulence in experimental endocarditis: a host defense role for platelet microbicidal proteins. Infect. Immun. 65, 4652?4660 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Palma, M., Shannon, O., Quezada, H. C., Berg, A. & Flock, J. I. Extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus blocks platelet aggregation due to its binding to the α-chain. J. Biol. Chem. 276, 31691?31697 (2001).

    Article  CAS  PubMed  Google Scholar 

  151. Shannon, O. & Flock, J. I. Extracellular fibrinogen binding protein, Efb, from Staphylococcus aureus binds to platelets and inhibits platelet aggregation. Thromb. Haemost. 91, 779?789 (2004).

    Article  CAS  PubMed  Google Scholar 

  152. Tran, U., Boyle, T., Shupp, J. W., Hammamieh, R. & Jett, M. Staphylococcal enterotoxin B initiates protein kinase C translocation and eicosanoid metabolism while inhibiting thrombin-induced aggregation in human platelets. Mol. Cell. Biochem. 21 Mar 2006 (doi:10.1007/s11010-006-9134-6).

  153. Alam, S., Gupta, M. & Bhatnagar, R. Inhibition of platelet aggregation by anthrax edema toxin. Biochem. Biophys. Res. Commun. 339, 107?114 (2006).

    Article  CAS  PubMed  Google Scholar 

  154. Kau, J. H. et al. Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets. J. Infect. Dis. 192, 1465?1474 (2005).

    Article  CAS  PubMed  Google Scholar 

  155. Iwaki, M., Kamachi, K., Heveker, N. & Konda, T. Suppression of platelet aggregation by Bordetella pertussis adenylate cyclase toxin. Infect. Immun. 67, 2763?2768 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Beck, J., Garcia, R., Heiss, G., Vokonas, P. S. & Offenbacher, S. Periodontal disease and cardiovascular disease. J. Periodontol. 67, 1123?1137 (1996).

    Article  CAS  PubMed  Google Scholar 

  157. Pihlstrom, B. L., Michalowicz, B. S. & Johnson, N. W. Periodontal diseases. Lancet 366, 1809?1820 (2005).

    Article  PubMed  Google Scholar 

  158. Spahr, A. et al. Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study. Arch. Intern. Med. 166, 554?559 (2006). Shows an association between periodontitis, oral pathogen burden and cardiovascular disease.

    Article  CAS  PubMed  Google Scholar 

  159. Haffajee, A. D. & Socransky, S. S. Microbial etiological agents of destructive periodontal diseases. Periodontol. 2000 5, 78?111 (1994).

    Article  CAS  PubMed  Google Scholar 

  160. Potempa, J. & Travis, J. Porphyromonas gingivalis proteinases in periodontitis, a review. Acta. Biochim. Pol. 43, 455?465 (1996).

    Article  CAS  PubMed  Google Scholar 

  161. Potempa, J., Banbula, A. & Travis, J. Role of bacterial proteinases in matrix destruction and modulation of host responses. Periodontol. 24, 153?192 (2000).

    Article  CAS  Google Scholar 

  162. Lourbakos, A. et al. Activation of protease-activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: a new trait in microbial pathogenicity. Blood 97, 3790?3797 (2001). Identifies a novel mechanism of bacteria-induced platelet activation involving a family of secreted proteases.

    Article  CAS  PubMed  Google Scholar 

  163. Coutinho, I. R., Berk, R. S. & Mammen, E. Platelet aggregation by a phospholipase C from Pseudomonas aeruginosa. Thromb. Res. 51, 495?505 (1988).

    Article  CAS  PubMed  Google Scholar 

  164. Kalia, N. et al. Studies on the gastric mucosal microcirculation. 2. Helicobacter pylori water soluble extracts induce platelet aggregation in the gastric mucosal microcirculation in vivo. Gut 41, 748?752 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Ohkuni, H. et al. Purification and partial characterization of a novel human platelet aggregation factor in the extracellular products of Streptococcus mitis, strain Nm-65. FEMS Immunol. Med. Microbiol. 17, 121?129 (1997).

    Article  CAS  PubMed  Google Scholar 

  166. Chia, J. S., Lin, Y. L., Lien, H. T. & Chen, J. Y. Platelet aggregation induced by serotype polysaccharides from Streptococcus mutans. Infect. Immun. 72, 2605?2617 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Barkalow, K. L. et al. Role for phosphoinositide 3-kinase in FcγRIIA-induced platelet shape change. Am. J. Physiol. Cell Physiol. 285, C797?C805 (2003).

    Article  CAS  PubMed  Google Scholar 

  168. Ragab, A. et al. The tyrosine phosphatase 1B regulates linker for activation of T-cell phosphorylation and platelet aggregation upon FcγRIIa cross-linking. J. Biol. Chem. 278, 40923?40932 (2003).

    Article  CAS  PubMed  Google Scholar 

  169. Cooney, D. S., Phee, H., Jacob, A. & Coggeshall, K. M. Signal transduction by human-restricted Fcγ RIIa involves three distinct cytoplasmic kinase families leading to phagocytosis. J. Immunol. 167, 844?854 (2001).

    Article  CAS  PubMed  Google Scholar 

  170. Usui, Y. et al. Platelet aggregation induced by strains of various species of coagulase-negative staphylococci. Microbiol. Immunol. 35, 15?26 (1991).

    Article  CAS  PubMed  Google Scholar 

  171. Guckian, J. C. Effect of pneumococci on blood clotting, platelets, and polymorphonuclear leukocytes. Infect. Immun. 12, 910?918 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Usui, Y., Ichiman, Y., Suganuma, M. & Yoshida, K. Platelet aggregation by strains of enterococci. Microbiol. Immunol. 35, 933?942 (1991).

    Article  CAS  PubMed  Google Scholar 

  173. Takii, R., Kadowaki, T., Baba, A., Tsukuba, T. & Yamamoto, K. A functional virulence complex composed of gingipains, adhesins, and lipopolysaccharide shows high affinity to host cells and matrix proteins and escapes recognition by host immune systems. Infect. Immun. 73, 883?893 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Kiley, P. & Holt, S. C. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect. Immun. 30, 862?873 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Willcox, M. D., Webb, B. C., Thakur, A. & Harty, D. W. Interactions between Candida species and platelets. J. Med. Microbiol. 47, 103?110 (1998).

    Article  CAS  PubMed  Google Scholar 

  176. Kalvegren, H., Majeed, M. & Bengtsson, T. Chlamydia pneumoniae binds to platelets and triggers P-selectin expression and aggregation: a causal role in cardiovascular disease? Arterioscler. Thromb. Vasc. Biol. 23, 1677?1683 (2003).

    Article  PubMed  CAS  Google Scholar 

  177. Czuprynski, C. J. & Balish, E. Interaction of rat platelets with Listeria monocytogenes. Infect. Immun. 33, 103?108 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We wish to acknowledge the Health Research Board of Ireland for supporting our research on bacteria?platelet interactions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy J. Foster.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Genome Project

Bacillus anthracis

Bordetella pertussis

Borrelia burgdorferi

Candida albicans

Campylobacter fetus

Chlamydophila pneumoniae

Escherichia. coli

Helicobacter pylori

Lactococcus lactis

Porphyromonas gingivalis

Pseudomonas aeruginosa

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus agalactiae

Streptococcus gordonii

Streptococcus mitis

Streptococcus pneumoniae

Streptococcus pyogenes

Streptococcus sanguinis

FURTHER INFORMATION

Timothy J. Foster's homepage

J. Ross Fitzgerald's homepage

Royal College of Surgeons in Ireland

Glossary

Infective endocarditis

The formation of an infected thrombus on one of the coronary valves.

Disseminated intravascular coagulation

Activation of coagulation in a diffuse manner, often in response to infection. Instead of leading to clot formation it results in consumption of coagulation factors, which can lead to bleeding problems.

Immune thrombocytopenia purpura

The formation of anti-platelet antibodies. Platelets with bound antibody are cleared from the circulation, resulting in a decreasing number of circulating platelets.

Myocardial infarction

The occlusion of one of the coronary vessels resulting in localized tissue damage, owing to lack of oxygen, and a heart attack.

Thrombus

The formation of a clot in a blood vessel, usually in response to injury. Thrombi can be either fibrin-rich, such as those that form in veins, or platelet-rich, which usually occur in the arterial system.

Thrombocytopenia

A drop in platelet count below the normal range, usually involving large decreases that result in bleeding problems.

Embolism

A fragment of a thrombus that breaks away and is carried to a distant blood vessel, which is then occluded.

Light transmission aggregometry

The standard method for measuring platelet activity, which is based on the principle that the absorption of a suspension of platelets is dependent on the number of particles. Platelet-rich plasma is stirred and an agonist is added. Platelet activation results in aggregate formation with a decrease in the number of particles and an increase in light transmission.

Atherosclerosis

An inflammation of the blood vessels usually associated with an influx of macrophages, deposition of cholesterol and formation of plaque. It results in the narrowing of blood vessels in key organs such as the heart and brain. If the plaque ruptures it triggers clot formation, resulting in a myocardial infarction or stroke.

Acute coronary syndrome

A syndrome characterized by decreased blood supply to the heart caused by the rupture of an atherosclerotic plaque. ACS covers the spectrum of unstable angina (chest pain at rest) to myocardial infarction.

Megakaryocytes

The bone marrow cells responsible for the production of platelets.

Fibrinogen

A soluble protein in plasma that is essential for clotting of blood. Soluble fibrinogen is converted to fibrin by the action of thrombin, and then polymerizes to form a clot.

von Willebrand factor

Also known as Factor VIII-related antigen. Important for platelet adhesion under shear at sites of endothelial damage. In blood, von Willebrand factor is multimeric with 10 or more monomers linked together; each monomer is a 220-kDa protein comprising four distinct domains.

Teichoic acid

A phosphate-rich, anionic polysaccharide attached to the peptidoglycan of Gram-positive bacteria.

Complement

A part of the innate immune system comprising serum proteins that can protect against infection.

Fc receptor

Surface molecules on various cells that bind to the Fc regions of immunoglobulins, thereby initiating antibody effector functions.

Fibronectin

A high-molecular-weight glycoprotein present in soluble form in plasma that binds to integrins and the extracellular matrix.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fitzgerald, J., Foster, T. & Cox, D. The interaction of bacterial pathogens with platelets. Nat Rev Microbiol 4, 445–457 (2006). https://doi.org/10.1038/nrmicro1425

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro1425

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing