title: The anchorless adhesin Eap (extracellular adherence protein) from Staphylococcus aureus selectively recognizes extracellular matrix aggregates but binds promiscuously to monomeric matrix macromolecules.
abstract: Besides a number of cell wall-anchored adhesins, the majority of Staphylococcus aureus strains produce anchorless, cell wall-associated proteins, such as Eap (extracellular adherence protein). Eap contains four to six tandem repeat (EAP)-domains. Eap mediates diverse biological functions, including adherence and immunomodulation, thus contributing to S. aureus pathogenesis. Eap binding to host macromolecules is unusually promiscuous and includes matrix or matricellular proteins as well as plasma proteins. The structural basis of this promiscuity is poorly understood. Here, we show that in spite of the preferential location of the binding epitopes within triple helical regions in some collagens there is a striking specificity of Eap binding to different collagen types. Collagen I, but not collagen II, is a binding substrate in monomolecular form. However, collagen I is virtually unrecognized by Eap when incorporated into banded fibrils. By contrast, microfibrils containing collagen VI as well as basement membrane-associated networks containing collagen IV, or aggregates containing fibronectin bound Eap as effectively as the monomeric proteins. Therefore, Eap-binding to extracellular matrix ligands is promiscuous at the molecular level but not indiscriminate with respect to supramolecular structures containing the same macromolecules. In addition, Eap bound to banded fibrils after their partial disintegration by matrix-degrading proteinases, including matrix metalloproteinase 1. Therefore, adherence to matrix suprastructures by S. aureus can be supported by inflammatory reactions.
authors.affiliation: University Hospital of Münster, Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstrasse 15, D-48149 Münster, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Hussain
authors.forename: Daniela
authors.initials: D
authors.lastname: Villone
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Bhanu
authors.initials: B
authors.lastname: Sinha
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000382:microbiology; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D013211:Staphylococcus aureus; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D046911:Macromolecular Substances; D016601:RNA-Binding Proteins