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It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The development of secondary infections is based on the bacterium\u2019s ability to associate with endothelial cells lining blood vessels. The success of endothelial colonization and infection by\n            <jats:italic>S. aureus<\/jats:italic>\n            relies on its ability to express a wide array of cell wall-anchored and secreted virulence factors. Establishment of endothelial infection by the pathogen is a multistep process involving adhesion, invasion, extravasation, and dissemination of the bacterium into surrounding tissues. The process is dependent on the type of endothelium in different organs (tissues) and pathogenetic potential of the individual strains. In this review, we report an update on the organization of the endothelium in the vessels, the structure and function of the virulence factors of S.\n            <jats:italic>aureus<\/jats:italic>\n            , and the several aspects of bacteria-endothelial cell interactions. After these sections, we will discuss recent advances in understanding the specific mechanisms of infections that develop in the heart, bone and joints, lung, and brain. Finally, we describe how neutrophils bind to endothelial cells, migrate to the site of infection to kill bacteria in the tissues, and how staphylococci counteract neutrophils\u2019 actions. Knowledge of the molecular details of\n            <jats:italic>S. aureus<\/jats:italic>\n            -endothelial cell interactions will promote the development of new therapeutic strategies and tools to combat this formidable pathogen.\n          <\/jats:p>","DOI":"10.1128\/cmr.00098-24","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T14:01:07Z","timestamp":1736863267000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["The endothelium at the interface between tissues and\n            <i>Staphylococcus aureus<\/i>\n            in the bloodstream"],"prefix":"10.1128","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-1604","authenticated-orcid":true,"given":"Pietro","family":"Speziale","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Unit of Biochemistry, University of Pavia","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3827-689X","authenticated-orcid":true,"given":"Timothy J.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Trinity College Dublin","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-0066","authenticated-orcid":false,"given":"Carla Renata","family":"Arciola","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology of Implant Infections, Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli","place":["Bologna, Italy"]},{"name":"Department of Medical and Surgical Sciences, University of Bologna","place":["Bologna, 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