{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:52:05Z","timestamp":1790513525145,"version":"4.1.0"},"reference-count":26,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Polish Ministry of Science and Higher Education","award":["N N301 050439"],"award-info":[{"award-number":["N N301 050439"]}]},{"name":"Polish Ministry of Science and Higher Education","award":["POIG.02.01.00-12-064\/08"],"award-info":[{"award-number":["POIG.02.01.00-12-064\/08"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["N N301 050439"],"award-info":[{"award-number":["N N301 050439"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["POIG.02.01.00-12-064\/08"],"award-info":[{"award-number":["POIG.02.01.00-12-064\/08"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>As a facultative intracellular pathogen,<jats:italic>Staphylococcus aureus<\/jats:italic>invades macrophages and then promotes the cytoprotection of infected cells thus stabilizing safe niche for silent persistence. This process occurs through the upregulation of crucial antiapoptotic genes, in particular,<jats:italic>myeloid cell leukemia-1 (MCL-1)<\/jats:italic>. Here, we investigated the underlying mechanism and signal transduction pathways leading to increased<jats:italic>MCL-1<\/jats:italic>expression in infected macrophages. Live<jats:italic>S. aureus<\/jats:italic>not only stimulated<jats:italic>de novo<\/jats:italic>synthesis of Mcl-1, but also prolonged the stability of this antiapoptotic protein. Consistent with this, we proved a crucial role of Mcl-1 in<jats:italic>S. aureus<\/jats:italic>-induced cytoprotection, since silencing of<jats:italic>MCL1<\/jats:italic>by siRNA profoundly reversed the cytoprotection of infected cells leading to apoptosis. Increased<jats:italic>MCL1<\/jats:italic>expression in infected cells was associated with enhanced NF<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>\u03ba<\/mml:mi><\/mml:mrow><\/mml:math>B activation and subsequent IL-6 secretion, since the inhibition of both NF<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mi>\u03ba<\/mml:mi><\/mml:mrow><\/mml:math>B and IL-6 signalling pathways abrogated Mcl-1 induction and cytoprotection. Finally, we confirmed our observation<jats:italic>in vivo<\/jats:italic>in murine model of septic arthritis showing the association between the severity of arthritis and Mcl-1 expression. Therefore, we propose that<jats:italic>S. aureus<\/jats:italic>is hijacking the Mcl-1-dependent inhibition of apoptosis to prevent the elimination of infected host cells, thus allowing the intracellular persistence of the pathogen, its dissemination by infected macrophages, and the progression of staphylococci diseases.<\/jats:p>","DOI":"10.1155\/2013\/427021","type":"journal-article","created":{"date-parts":[[2013,1,28]],"date-time":"2013-01-28T23:49:27Z","timestamp":1359416967000},"page":"1-12","source":"Crossref","is-referenced-by-count":18,"title":["The Role of Mcl-1 in<i>S. aureus<\/i>-Induced Cytoprotection of Infected Macrophages"],"prefix":"10.1155","volume":"2013","author":[{"given":"Joanna","family":"Koziel","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kmiecik","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Chmiest","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Maresz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Mizgalska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Maciag-Gudowska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Mydel","sequence":"additional","affiliation":[{"name":"Broegelmann Research Laboratory, The Gade Institute, University of Bergen, 50021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Krak\u00f3w, Poland"},{"name":"Oral Health and Systemic Diseases Research Group, School of Dentistry, University of Louisville, Louisville, KY 40204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"98","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"issue":"6","key":"2","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.4049\/jimmunol.175.6.3907","volume":"175","year":"2005","journal-title":"Journal of Immunology"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001409"},{"issue":"7","key":"4","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1128\/IAI.67.7.3512-3517.1999","volume":"67","year":"1999","journal-title":"Infection and Immunity"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2004.00444.x"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1538"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005210"},{"issue":"8","key":"8","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1073\/pnas.90.8.3516","volume":"90","year":"1993","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411434200"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/sj\/leu\/2402416"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07273.x"},{"issue":"9","key":"13","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1182\/blood.V92.9.3226","volume":"92","year":"1998","journal-title":"Blood"},{"issue":"2","key":"14","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1182\/blood.V89.2.630","volume":"89","year":"1997","journal-title":"Blood"},{"issue":"1","key":"15","first-page":"5","volume":"10","year":"1983","journal-title":"Journal of Rheumatology"},{"issue":"4","key":"16","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/anr.1780320422","volume":"32","year":"1989","journal-title":"Arthritis and Rheumatism"},{"issue":"8","key":"17","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1128\/IAI.59.8.2615-2623.1991","volume":"59","year":"1991","journal-title":"Infection and Immunity"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199912)29:12<3945::AID-IMMU3945>3.0.CO;2-O"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.03.008"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00412-3"},{"issue":"9","key":"21","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.4049\/jimmunol.176.9.5529","volume":"176","year":"2006","journal-title":"Journal of Immunology"},{"issue":"1","key":"22","doi-asserted-by":"crossref","first-page":"430","DOI":"10.4049\/jimmunol.170.1.430","volume":"170","year":"2003","journal-title":"Journal of Immunology"},{"issue":"5","key":"23","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1189\/jlb.70.5.783","volume":"70","year":"2001","journal-title":"Journal of Leukocyte Biology"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.128.6.1173"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400758"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200521766"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2013\/427021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2013\/427021.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2013\/427021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:27Z","timestamp":1687999287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/mi\/2013\/427021\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":26,"alternative-id":["427021","427021"],"URL":"https:\/\/doi.org\/10.1155\/2013\/427021","relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}