Recent work has shown that coagulation and innate immunity are tightly interwoven host responses that help eradicate an invading pathogen. Some bacterial species, including , secrete pro-coagulant factors that, in turn, can modulate these immune reactions. Such mechanisms may not only protect the micro-organism from a lethal attack, but also promote bacterial proliferation and the establishment of infection. Our data showed that coagulase-positive bacteria promoted clotting of plasma which was not seen when a coagulase-deficient mutant strain was used. Furthermore, studies showed that this ability constituted a mechanism that supported the aggregation, survival and persistence of the micro-organism within the fibrin network. These findings were also confirmed when agglutination and persistence of coagulase-positive bacteria at the local focus of infection were studied in a subcutaneous murine infection model. In contrast, the coagulase-deficient strain which was not able to induce clotting failed to aggregate and to persist . In conclusion, our data suggested that coagulase-positive have evolved mechanisms that prevent their elimination within a fibrin clot.


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  1. Angus D. C., van der Poll T.(2013). Severe sepsis and septic shock. N Engl J Med 369, 840851. [View Article][PubMed] [Google Scholar]
  2. Bancroft J. D., Gamble M.(2002).Theory and Practice of Histological Techniques. New York: Churchill Livingstone. [Google Scholar]
  3. Blevins S. M., Bronze M. S.(2010). Robert Koch and the ‘golden age’ of bacteriology. Int J Infect Dis 14, e744e751. [View Article][PubMed] [Google Scholar]
  4. Bokarewa M. I., Jin T., Tarkowski A.(2006). Staphylococcus aureus: staphylokinase. Int J Biochem Cell Biol 38, 504509. [View Article][PubMed] [Google Scholar]
  5. Cheng A. G., McAdow M., Kim H. K., Bae T., Missiakas D. M., Schneewind O.(2010). Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog 6, e1001036. [View Article][PubMed] [Google Scholar]
  6. Cheung A. L., Chien Y. T., Bayer A. S.(1999). Hyperproduction of alpha-hemolysin in a sigB mutant is associated with elevated SarA expression in Staphylococcus aureus. Infect Immun 67, 13311337.[PubMed] [Google Scholar]
  7. Engelmann B., Massberg S.(2013). Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13, 3445. [View Article][PubMed] [Google Scholar]
  8. Field H. I., Smith H. W.(1945). Coagulase test for staphylococci. J Comp Pathol 55, 6369. [View Article] [Google Scholar]
  9. Friedrich R., Panizzi P., Fuentes-Prior P., Richter K., Verhamme I., Anderson P. J., Kawabata S., Huber R., Bode W., Bock P. E.(2003). Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. Nature 425, 535539. [View Article][PubMed] [Google Scholar]
  10. Goerke C., Fluckiger U., Steinhuber A., Zimmerli W., Wolz C.(2001). Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the induction of α-toxin during device-related infection resolved by direct quantitative transcript analysis. Mol Microbiol 40, 14391447. [View Article][PubMed] [Google Scholar]
  11. Guggenberger C., Wolz C., Morrissey J. A., Heesemann J.(2012). Two distinct coagulase-dependent barriers protect Staphylococcus aureus from neutrophils in a three dimensional in vitro infection model. PLoS Pathog 8, e1002434. [View Article][PubMed] [Google Scholar]
  12. Haslinger-Löffler B., Kahl B. C., Grundmeier M., Strangfeld K., Wagner B., Fischer U., Cheung A. L., Peters G., Schulze-Osthoff K., Sinha B.(2005). Multiple virulence factors are required for Staphylococcus aureus-induced apoptosis in endothelial cells. Cell Microbiol 7, 10871097. [View Article][PubMed] [Google Scholar]
  13. Horsburgh M. J., Aish J. L., White I. J., Shaw L., Lithgow J. K., Foster S. J.(2002). σB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184, 54575467. [View Article][PubMed] [Google Scholar]
  14. Lebeau C., Vandenesch F., Greenland T., Novick R. P., Etienne J.(1994). Coagulase expression in Staphylococcus aureus is positively and negatively modulated by an agr-dependent mechanism. J Bacteriol 176, 55345536.[PubMed] [Google Scholar]
  15. Loof T. G., Mörgelin M., Johansson L., Oehmcke S., Olin A. I., Dickneite G., Norrby-Teglund A., Theopold U., Herwald H.(2011). Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense. Blood 118, 25892598. [View Article][PubMed] [Google Scholar]
  16. Mattsson E., Herwald H., Cramer H., Persson K., Sjöbring U., Björck L.(2001). Staphylococcus aureus induces release of bradykinin in human plasma. Infect Immun 69, 38773882. [View Article][PubMed] [Google Scholar]
  17. McAdow M., Missiakas D. M., Schneewind O.(2012). Staphylococcus aureus secretes coagulase and von Willebrand factor binding protein to modify the coagulation cascade and establish host infections. J Innate Immun 4, 141148. [View Article][PubMed] [Google Scholar]
  18. McDevitt D., Vaudaux P., Foster T. J.(1992). Genetic evidence that bound coagulase of Staphylococcus aureus is not clumping factor. Infect Immun 60, 15141523.[PubMed] [Google Scholar]
  19. Much H.(1908). Über eine Vorstufe des Fibrinfermentes in Kulturen von Staphylokokkus aureus. Biochem Z 14, 143 (in German). [Google Scholar]
  20. Nippe N., Varga G., Holzinger D., Löffler B., Medina E., Becker K., Roth J., Ehrchen J. M., Sunderkötter C.(2011). Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response. J Invest Dermatol 131, 125132. [View Article][PubMed] [Google Scholar]
  21. Nordin S. L., Andersson C., Bjermer L., Bjartell A., Mörgelin M., Egesten A.(2013). Midkine is part of the antibacterial activity released at the surface of differentiated bronchial epithelial cells. J Innate Immun 5, 519530. [View Article][PubMed] [Google Scholar]
  22. Novick R. P.(1967). Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology 33, 155166. [View Article][PubMed] [Google Scholar]
  23. Peng H. L., Novick R. P., Kreiswirth B., Kornblum J., Schlievert P.(1988). Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol 170, 43654372.[PubMed] [Google Scholar]
  24. Phonimdaeng P., O’Reilly M., Nowlan P., Bramley A. J., Foster T. J.(1990). The coagulase of Staphylococcus aureus 8325-4. Sequence analysis and virulence of site-specific coagulase-deficient mutants. Mol Microbiol 4, 393404. [View Article][PubMed] [Google Scholar]
  25. Vanassche T., Verhaegen J., Peetermans W. E., Van Ryn J., Cheng A., Schneewind O., Hoylaerts M. F., Verhamme P.(2011). Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence. J Thromb Haemost 9, 24362446. [View Article][PubMed] [Google Scholar]
  26. Wang X., Lin X., Loy J. A., Tang J., Zhang X. C.(1998). Crystal structure of the catalytic domain of human plasmin complexed with streptokinase. Science 281, 16621665. [View Article][PubMed] [Google Scholar]

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