{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:41:42Z","timestamp":1793346102452,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["13\/CDA\/2119"],"award-info":[{"award-number":["13\/CDA\/2119"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A\/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% \u00b1 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 \u00b1 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia.<\/jats:p>","DOI":"10.3390\/antibiotics10050581","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T10:54:22Z","timestamp":1620989662000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5876-8096","authenticated-orcid":false,"given":"Danielle","family":"Nader","sequence":"first","affiliation":[{"name":"Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fajer","family":"Yousef","sequence":"additional","affiliation":[{"name":"Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict K.","family":"Ryan","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Kerrigan","sequence":"additional","affiliation":[{"name":"Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, 123 St. Stephens Green, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1001\/jama.2015.1410","article-title":"Readmission diagnoses after hospitalization for severe sepsis and other acute medical conditions","volume":"313","author":"Prescott","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S2468-1253(16)30119-4","article-title":"The role of the gut microbiota in sepsis","volume":"2","author":"Haak","year":"2017","journal-title":"Lancet Gastroenterol. 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