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Extracellular Adherence Protein from Staphylococcus aureus Enhances Internalization into Eukaryotic Cells

Department of Laboratory Medicine,¹ Department of Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden,⁴ Institute of Medical Microbiology, University of Muenster Hospital, D-48129 Muenster,² Institute of Microbiology and Hygiene, University of Saarland Hospital, D-66421 Homburg/Saar, Germany³

Received 30 April 2002/ Returned for modification 25 July 2002/ Accepted 6 February 2003

In this study we have shown that Eap (extracellular adherence protein) plays a role in the internalization process of Staphylococcus aureus into eukaryotic cells. Eap is a protein that is mostly extracellularly and to a lesser extent is bound to the bacterial surface as a result of rebinding. Eap is able to bind to several plasma proteins, such as fibronectin, fibrinogen, and prothrombin. It has the capacity to form oligomers and is able to agglutinate S. aureus. A mutant strain, Newman mAH12 (eap:: Ery^r), with a deficient eap gene was used in the present study. We have demonstrated that (i) strain Newman mAH12 could adhere to and become internalized to a higher extent by eukaryotic cells than the isogenic mutant, (ii) strain Newman mAH12 complemented with the eap gene displayed restoration of the internalization level, (iii) externally added Eap enhanced the internalization of laboratory and clinical S. aureus strains as well as of S. carnosus (a coagulase-negative species devoid of proteins important for internalization), and (iv) antibodies against Eap were able to block the internalization process in strain Newman mAH12 and clinical isolates. Eap, with its broad binding capacity and its surface localization, thus seems to contribute to the internalization of S. aureus into eukaryotic cells. We therefore propose a novel internalization pathway for S. aureus in which Eap plays an enhancing role.

Editor: V. J. DiRita

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