{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:08:43Z","timestamp":1792058923562,"version":"4.4.0"},"reference-count":25,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R01AT007318"],"award-info":[{"award-number":["R01AT007318"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA025379"],"award-info":[{"award-number":["AA025379"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM145845"],"award-info":[{"award-number":["R01GM145845"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"crossref","award":["GR089825"],"award-info":[{"award-number":["GR089825"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic multidrug-resistant bacterial infections have become a global public health priority due to the diminished efficacy of standard antibiotic regimens and can lead to sepsis, which is among the leading causes of death (11 million\/year) and years of lost life worldwide. We report an effective and well-defined antibiotic equimolar mixture of the platanosides 1\u20134 that is as effective as its constituent parts and is active against multidrug-resistant Staphylococcus and Streptococcus spp. The platanosides can be easily and inexpensively manufactured in good purity from sycamore tree (Platanus spp.) leaves, making them a viable option as a drug to control multidrug-resistant infections in low- and middle-income countries. The platanosides 1\u20134 exhibited activity against clinically derived Staphylococcus aureus (methicillin-resistant, vancomycin-resistant, and vancomycin-intermediate) with minimal inhibitory concentration values of 0.5\u201316 \u03bcg\/mL. The minimal inhibitory concentration values against clinically derived Streptococcus spp. were 2, 1, 0.06, and 1 \u03bcg\/mL against Streptococcus mitis, Streptococcus paramsanginis, Streptococcus gordonii, and Streptococcus pneumoniae, respectively. Time-kill studies of the platanosides are reported. The proposed molecular targets and unique polypharmacology of the platanosides 1\u20134 are also discussed.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00028","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:43:06Z","timestamp":1784317386000},"page":"2642-2649","source":"Crossref","is-referenced-by-count":1,"title":["Platanosides, a Promising Class of Plant-Derived Antibiotics,\nAre Effective against a Suite of Clinically Derived MDR and Drug-Sensitive\n                    <i>Staph<\/i>\n                    and\n                    <i>Strep<\/i>\n                    spp."],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-4438","authenticated-orcid":true,"given":"Cody F.","family":"Dickinson","sequence":"first","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-3405","authenticated-orcid":true,"given":"Menny M.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-0767","authenticated-orcid":true,"given":"Ahmed","family":"Alford","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope L.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geehan","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Henry Ford Health , , , ,","place":["Detroit, Michigan, United States, 48202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryssa","family":"Trupiano","sequence":"additional","affiliation":[{"name":"Henry Ford Health , , , ,","place":["Detroit, Michigan, United States, 48202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britney","family":"Aldrich","sequence":"additional","affiliation":[{"name":"Henry Ford Health , , , ,","place":["Detroit, Michigan, United States, 48202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A.","family":"Valeriote","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Henry Ford Hospital , , , ,","place":["Detroit, Michigan, United States, 48202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Arosemena","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Bialousow","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhong","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7092-8993","authenticated-orcid":true,"given":"Marcus A.","family":"Tius","sequence":"additional","affiliation":[{"name":"University of Hawaii at Manoa , , , ,","place":["Honolulu, Hawaii, United States, 96822"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-5898","authenticated-orcid":true,"given":"Yeun-Mun","family":"Choo","sequence":"additional","affiliation":[{"name":"University of Malaya , , ,","place":["Kuala Lumpur, Malaysia, 50603"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Lemasters","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-4002","authenticated-orcid":true,"given":"Mark T.","family":"Hamann","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina , , , ,","place":["Charleston, South Carolina, United States, 29425"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"issue":"5","key":"2026081410071913100_cit1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S1473-3099(09)70066-0","article-title":"Gram-positive toxic shock syndromes","volume":"9","author":"Lappin","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"2026081410071913100_cit2","volume-title":"Antibiotic Resistance\nThreats in the United States","author":"CDC.","year":"2019"},{"issue":"10219","key":"2026081410071913100_cit3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global,\nregional, and national sepsis incidence and mortality, 1990\u20132017:\nanalysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"issue":"1","key":"2026081410071913100_cit4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08881-y","article-title":"Cost of\npostoperative sepsis in Vietnam","volume":"12","author":"Bui","year":"2022","journal-title":"Sci. Rep."},{"issue":"4","key":"2026081410071913100_cit5","doi-asserted-by":"publisher","DOI":"10.3390\/medicines5040121","article-title":"The Phytochemistry\nof Cherokee Aromatic Medicinal Plants","volume":"5","author":"Setzer","year":"2018","journal-title":"Medicines"},{"key":"2026081410071913100_cit6","unstructured":"Hutton, K.\n          \n          A comparative\nstudy of the plants used for medicinal purposes by the Creek and Seminoles\ntribes, Theses and Dissertations; USF Tampa, USF Tampa Graduate2010https:\/\/digitalcommons.usf.edu\/etd\/1665."},{"key":"2026081410071913100_cit7","unstructured":"Ibrahim, M. A.\n          \n          Isolation and\nMedicinal Chemistry of Leads Acting on Infectious Diseases and Neurological\nTargets, Dissertation; University\nof Mississippi2011."},{"issue":"12","key":"2026081410071913100_cit8","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1021\/np900499q","article-title":"Methicillin-resistant Staphylococcus aureus (MRSA)-active metabolites from Platanus occidentalis (American sycamore)","volume":"72","author":"Ibrahim","year":"2009","journal-title":"J. Nat. Prod."},{"key":"2026081410071913100_cit9","unstructured":"Hamann, M. T.; Ibrahim, M. A.\n          Methicillin-resistant Staphylococcus aureus active metabolites US 2010. US2010\/0273726A1, 2010."},{"issue":"7","key":"2026081410071913100_cit10","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1021\/acs.jnatprod.2c00324","article-title":"Platanosides,\na potential botanical drug combination, decrease liver injury caused\nby acetaminophen overdose in mice","volume":"85","author":"Samuvel","year":"2022","journal-title":"J. Nat. Prod."},{"issue":"1","key":"2026081410071913100_cit11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2169\/internalmedicine.7192-21","article-title":"Extremely Elevated Procalcitonin\nin a Case of Acetaminophen Overdose and Acute Liver Injury","volume":"61","author":"Nishimura","year":"2022","journal-title":"Int. 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Pharmacol."},{"issue":"3","key":"2026081410071913100_cit16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s43016-021-00243-7","article-title":"Network\nmedicine framework shows that proximity of polyphenol targets and\ndisease proteins predicts therapeutic effects of polyphenols","volume":"2","author":"do Valle","year":"2021","journal-title":"Nat. Food"},{"issue":"10","key":"2026081410071913100_cit17","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9546.1000364","article-title":"Antibacterial Activities of Metabolites\nfrom Platanus occidentalis (American\nsycamore) against\nFish Pathogenic Bacteria","volume":"06","author":"Schrader","year":"2015","journal-title":"J. Aquac. Res. 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Antibiot."},{"issue":"8","key":"2026081410071913100_cit20","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1002\/phar.2806","article-title":"Current therapies\nand challenges for the treatment\nof Staphylococcus aureus biofilm-related\ninfections","volume":"43","author":"Tran","year":"2023","journal-title":"Pharmacotherapy"},{"key":"2026081410071913100_cit21","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.phytol.2024.10.001","article-title":"High-value\nflavonoids with potential\nanti-inflammatory benefits from Platanus \u00d7 acerifolia Willd leaves:\nTurning waste into treasure","volume":"64","author":"Wu","year":"2024","journal-title":"Phytochem. Lett."},{"key":"2026081410071913100_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107103","article-title":"Platanosides from\nPlatanus \u00d7 acerifolia: New molecules, SAR,\nand target validation of a strong lead for drug-resistant bacterial\ninfections and the associated sepsis","volume":"143","author":"Wu","year":"2024","journal-title":"Bioorg.\nChem."},{"issue":"5","key":"2026081410071913100_cit23","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1093\/jac\/dks005","article-title":"Novel inhibitory\nactivity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea\nlingue Nees","volume":"67","author":"Holler","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"issue":"3","key":"2026081410071913100_cit24","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1248\/bpb.32.489","article-title":"Synergistic effect\nof kaempferol glycosides purified from Laurus nobilis and fluoroquinolones\non methicillin-resistant Staphylococcus aureus","volume":"32","author":"Liu","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"2026081410071913100_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.103539","article-title":"The anti-MRSA compound 3-O-alpha-L-(2\n\u2033, 3 \u2033-di-p-coumaroyl)\nrhamnoside (KCR) inhibits protein synthesis in Staphylococcus aureus","volume":"210","author":"Carruthers","year":"2020","journal-title":"J. Proteomics"}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.6c00028","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/8\/2642\/66014618\/acsinfecdis.6c00028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/8\/2642\/66014618\/acsinfecdis.6c00028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:16:47Z","timestamp":1786717007000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/12\/8\/2642\/5214757\/Platanosides-a-Promising-Class-of-Plant-Derived"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":25,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,7,17]]},"published-print":{"date-parts":[[2026,8,14]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.6c00028","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}