{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:06:26Z","timestamp":1792613186450,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative <jats:bold>6i<\/jats:bold> as a promising agent with significant antibacterial activity against <jats:italic>S. aureus<\/jats:italic> and clinical MRSA isolates (MIC\u2009=\u20092\u20138\u2009\u03bcg\/mL), showing high membrane selectivity. Unlike traditional antibiotics, <jats:bold>6i<\/jats:bold> demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance. Compound <jats:bold>6i<\/jats:bold> also could inhibit biofilm formation and eradicate bacteria within biofilms. Mechanistic studies further revealed that <jats:bold>6i<\/jats:bold> could target bacterial cell membranes, disrupting the integrity of the cell membrane and leading to increased DNA leakage, resulting in potent antibacterial effects. Meanwhile, <jats:bold>6i<\/jats:bold> also showed good plasma stability and excellent biosafety. Notably, <jats:bold>6i<\/jats:bold> displayed good <jats:italic>in vivo<\/jats:italic> antibacterial activity in a mouse skin abscess model of MRSA-16 infection, which was comparable to the positive control vancomycin. These findings indicated that the magnolol derivative <jats:bold>6i<\/jats:bold> possessed the potential to be a novel anti-MRSA infection agent.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1385585","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T11:40:37Z","timestamp":1715946037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["A membrane-targeting magnolol derivative for the treatment of methicillin-resistant Staphylococcus aureus infections"],"prefix":"10.3389","volume":"15","author":[{"given":"Fushan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buhui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangshang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3289","DOI":"10.2147\/DDDT.S307113","article-title":"Imidazole as a promising medicinal scaffold: current status and future direction","volume":"15","author":"Alghamdi","year":"2021","journal-title":"Drug Des. 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Agents"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41579-022-00820-y","article-title":"Molecular mechanisms of antibiotic resistance revisited","volume":"21","author":"Darby","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1128\/AAC.01285-10","article-title":"Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study","volume":"55","author":"Farrell","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"12538","DOI":"10.1074\/jbc.R115.707547","article-title":"What\u2019s on the outside matters: the role of the extracellular polymeric substance of gram-negative biofilms in evading host immunity and as a target for therapeutic intervention*","volume":"291","author":"Gunn","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"12903","DOI":"10.1021\/acs.jmedchem.1c01073","article-title":"Development of membrane-active Honokiol\/Magnolol Amphiphiles as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)","volume":"64","author":"Guo","year":"","journal-title":"J. Med. Chem."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"104824","DOI":"10.1016\/j.bioorg.2021.104824","article-title":"Triphenyl-sesquineolignan analogues derived from Illicium simonsii maxim exhibit potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) by disrupting bacterial membranes","volume":"110","author":"Guo","year":"","journal-title":"Bioorg. Chem."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.2147\/IDR.S412308","article-title":"Progress in the prevalence, classification and drug resistance mechanisms of methicillin-resistant Staphylococcus aureus","volume":"16","author":"Hou","year":"2023","journal-title":"Infect. 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Chem."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"eaau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial peptides: application informed by evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e202202985","DOI":"10.1002\/chem.202202985","article-title":"Long-wavelength light-emitting electrochemical cells: materials and device engineering","volume":"29","author":"Lin","year":"2023","journal-title":"Chemistry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"104915","DOI":"10.1016\/j.micpath.2021.104915","article-title":"Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: a comprehensive review","volume":"156","author":"Liu","year":"2021","journal-title":"Microb. 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Chem."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1080\/14787210.2021.1951705","article-title":"Antimicrobial resistance in low-and middle-income countries: current status and future directions","volume":"20","author":"Sulis","year":"2022","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"10138","DOI":"10.1039\/C8TC03689F","article-title":"Recent development of phenanthroimidazole-based fluorophores for blue organic light-emitting diodes (OLEDs): an overview","volume":"6","author":"Tagare","year":"2018","journal-title":"J. Mater. Chem. C"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1021\/acs.jnatprod.7b00619","article-title":"Phenanthrenes: a promising group of plant secondary metabolites","volume":"81","author":"T\u00f3th","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1128\/AAC.49.6.2474-2478.2005","article-title":"Mechanisms of antibacterial action of three monoterpenes","volume":"49","author":"Trombetta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1080\/14786419.2017.1332606","article-title":"Phenanthrenes from Arundina graminifolia and in vitro evaluation of their antibacterial and anti-haemolytic properties","volume":"32","author":"Yan","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1021\/np200788u","article-title":"Phenanthrene derivatives from Cymbidium great flower Marie Laurencin and their biological activities","volume":"75","author":"Yoshikawa","year":"2012","journal-title":"J. Nat. 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