The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms.

نویسندگان

  • Athanasios N Athanasopoulos
  • Matina Economopoulou
  • Valeria V Orlova
  • Astrid Sobke
  • Darius Schneider
  • Holger Weber
  • Hellmut G Augustin
  • Sabine A Eming
  • Uwe Schubert
  • Thomas Linn
  • Peter P Nawroth
  • Muzaffar Hussain
  • Hans-Peter Hammes
  • Mathias Herrmann
  • Klaus T Preissner
  • Triantafyllos Chavakis
چکیده

Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus-infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presence of wild-type S aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alphav-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S aureus-infected wounds. Eap may also serve as a lead compound for new anti-inflammatory and antiangiogenic therapies in several pathologies.

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منابع مشابه

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms

Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus–infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presen...

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Transcription analysis of the extracellular adherence protein from Staphylococcus aureus in authentic human infection and in vitro.

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The eap Gene as a Novel Target for Specific Identification of Staphylococcus aureus

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عنوان ژورنال:
  • Blood

دوره 107 7  شماره 

صفحات  -

تاریخ انتشار 2006