title: The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms.
abstract: 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.
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Center Dr, Rm 4B17, Bethesda, MD 20892, USA.
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Athanasopoulos
authors.forename: Matina
authors.initials: M
authors.lastname: Economopoulou
authors.forename: Valeria V
authors.initials: VV
authors.lastname: Orlova
authors.forename: Astrid
authors.initials: A
authors.lastname: Sobke
authors.forename: Darius
authors.initials: D
authors.lastname: Schneider
authors.forename: Holger
authors.initials: H
authors.lastname: Weber
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
authors.forename: Sabine A
authors.initials: SA
authors.lastname: Eming
authors.forename: Uwe
authors.initials: U
authors.lastname: Schubert
authors.forename: Thomas
authors.initials: T
authors.lastname: Linn
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Hussain
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016384:Consensus Sequence; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D017353:Gene Deletion; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D014471:Umbilical Veins; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000382:microbiology / Q000503:physiopathology*
chemical_list: D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D018799:Intercellular Adhesion Molecule-1