{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:03:58Z","timestamp":1783350238657,"version":"3.54.6"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Ludwig Institute for Cancer Research"},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Salus Sanguinis"},{"name":"Les avions de S\u00e9bastien"},{"name":"Actions de recherche Concert\u00e9e","award":["16\/21-073"],"award-info":[{"award-number":["16\/21-073"]}]},{"name":"Wel research Institute Welbio","award":["F 44\/8\/5 - MCF\/UIG - 10955"],"award-info":[{"award-number":["F 44\/8\/5 - MCF\/UIG - 10955"]}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"crossref","award":["INCA-PLBIO-2015"],"award-info":[{"award-number":["INCA-PLBIO-2015"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes\n              <jats:italic>ex vivo<\/jats:italic>\n              and alter, in parallel, the activity of mitochondrial cytochrome\n              <jats:italic>c<\/jats:italic>\n              -oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+\/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00533-24","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T13:02:42Z","timestamp":1726750962000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Oxazolidinone antibiotics impair\n            <i>ex vivo<\/i>\n            megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets"],"prefix":"10.1128","volume":"68","author":[{"given":"Tamara V.","family":"Milosevic","sequence":"first","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Vertenoeil","sequence":"additional","affiliation":[{"name":"Signal Transduction and Molecular Hematology Unit (SIGN), de Duve Institute, Universit\u00e9 catholique de Louvain (UCLouvain), Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Vainchenker","sequence":"additional","affiliation":[{"name":"UMR 1170, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 de Paris-Sud &amp; Institut Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-3623","authenticated-orcid":true,"given":"Paul M.","family":"Tulkens","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan N.","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Signal Transduction and Molecular Hematology Unit (SIGN), de Duve Institute, Universit\u00e9 catholique de Louvain (UCLouvain), Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, Brussels, Belgium"},{"name":"WELBIO Department, WEL Research Institute, Wavre, Belgium"},{"name":"Nuffield Department of Medicine, Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-7991","authenticated-orcid":true,"given":"Fran\u00e7oise","family":"Van Bambeke","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","first-page":"181","article-title":"Linezolid pharmacia corp","volume":"1","author":"Barrett JF","year":"2000","unstructured":"Barrett JF. 2000. Linezolid pharmacia corp. Curr Opin Investig Drugs 1:181\u2013187.","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_3_5_3_2","first-page":"513","article-title":"Three new agents added to the arsenal to fight MRSA","volume":"67","author":"Strain J","year":"2014","unstructured":"Strain J. 2014. Three new agents added to the arsenal to fight MRSA. S D Med 67:513\u2013514.","journal-title":"S D Med"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.11.1010.34517"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028018783498"},{"key":"e_1_3_5_6_2","unstructured":"Anonymous. ZYVOX - linezolid injection solution - prescribing information. Pharmacia and Upjohn Company Division of Pfizer Inc NY NY. Available from: http:\/\/labeling.pfizer.com\/showlabeling.aspx?id=649. Accessed 1 May 2023"},{"key":"e_1_3_5_7_2","unstructured":"Anonymous. SIVEXTRO (tedizolid phosphate) for injection for intravenous use - prescribing information. White House Station NJ. Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc White House Station NJ. Available from: https:\/\/www.merck.com\/product\/usa\/pi_circulars\/s\/sivextro\/sivextro_pi.pdf. Accessed 1 May 2023"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.8.2723-2726.2002"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-010-0080-6"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.02.019"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01885-13"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1C361"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13262"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01185-10"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03684-14"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2019.07.021"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01599-17"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/501356"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01411-05"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.04.005"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3896-3902.2005"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-782-3:293"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2017.10.001"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-060-7_7"},{"key":"e_1_3_5_25_2","unstructured":"Anonymous. Antimicrobial wild type distributions of microorganisms. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Available from: https:\/\/mic.eucast.org\/Eucast2\/. Accessed 1 May 2023"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2011.608712"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg253"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00003"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201304054"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008670"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.253"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-718544"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.059"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00542-17"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.10.26"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114881"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2017.1335305"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00859-08"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00663-10"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10010053"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac028"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01282-23"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2021.1956461"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw206"},{"key":"e_1_3_5_45_2","unstructured":"Anonymous. 2019. Human Colony-Forming Unit (CFU) Assays Using MethoCult. Stemcell Technologies Vancouver BC Canada. Available from: https:\/\/www.stemcell.com\/media\/files\/manual\/MA28404-Human_Colony_Forming_Unit_Assays_Using_MethoCult.pdf. Retrieved 28 Mar 2019."},{"key":"e_1_3_5_46_2","unstructured":"Anonymous. 2019. MegaCult-C Assays for Quantitation of Human and Mouse Megakaryocytic Progenitor Cells. Stemcell Technologies Vancouver BC Canada. Available from: https:\/\/cdn.stemcell.com\/media\/files\/manual\/MA28413-MegaCult_C_Assays_Quantitation_Human_Mouse_Megakaryocytic_Progenitors.pdf. Retrieved 18 Mar 2019."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00533-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00533-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T15:44:55Z","timestamp":1728402295000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00533-24"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10,8]]}},"alternative-id":["10.1128\/aac.00533-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.00533-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"2024-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00533-24"}}