Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia. Academic Article uri icon


  • Fibrinogen can support host antimicrobial containment/clearance mechanisms, yet selected pathogens appear to benefit from host procoagulants to drive bacterial virulence. Here, we explored the hypothesis that host fibrin(ogen), on balance, supports Staphylococcus aureus infection in the context of septicemia. Survival studies following intravenous infection in control and fibrinogen-deficient mice established the overall utility of host fibrin(ogen) to S. aureus virulence. Complementary studies in mice expressing mutant forms of fibrinogen-retaining clotting function, but lacking either the bacterial ClfA (Fib(5)) binding motif or the host leukocyte integrin receptor M2 (Fib(390-396A)) binding motif, revealed the preeminent importance of the bacterial ClfA-fibrin(ogen) interaction in determining host survival. Studies of mice lacking platelets or the platelet integrin receptor subunit IIb established that the survival benefits observed in Fib(5) mice were largely independent of platelet IIb3-mediated engagement of fibrinogen. Fib(5) mice exhibited reduced bacterial burdens in the hearts and kidneys, a blunted host proinflammatory cytokine response, diminished microscopic tissue damage, and significantly diminished plasma markers of cardiac and other organ damage. These findings indicate that host fibrin(ogen) and bacterial ClfA are dual determinants of virulence and that therapeutic interventions at the level of fibrinogen could be advantageous in S. aureus septicemia.

published proceedings

  • Blood

altmetric score

  • 1

author list (cited authors)

  • Flick, M. J., Du, X., Prasad, J. M., Raghu, H., Palumbo, J. S., Smeds, E., Hk, M., & Degen, J. L.

citation count

  • 61

complete list of authors

  • Flick, Matthew J||Du, XinLi||Prasad, Joni M||Raghu, Harini||Palumbo, Joseph S||Smeds, Emanuel||Höök, Magnus||Degen, Jay L

publication date

  • March 2013

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