{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:11:28Z","timestamp":1783649488618,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council"},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP1144303"],"award-info":[{"award-number":["APP1144303"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP2002921"],"award-info":[{"award-number":["APP2002921"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Preservation and augmentation of existing antimicrobials is crucial in combating antimicrobial resistance. Gram-positive bacteria, exemplified by Staphylococcus aureus, are among the most common human bacterial pathogens, with methicillin-resistant S. aureus (MRSA) now established globally. Daptomycin is a last-line anti-staphylococcal antimicrobial that uniquely targets the bacterial membrane with bactericidal effects. Here, we developed lipid-based nanoparticles, namely cubosomes, to encapsulate daptomycin for targeted delivery via lipid-mediated interactions. Daptomycin-loaded cubosomes synergistically killed 14 clinical MRSA isolates in vitro compared with daptomycin or cubosomes alone. This synergy between daptomycin and cubosome was mediated by cubosomes docking on the S. aureus cell surface, releasing daptomycin for membrane extraction and penetration, followed by lipid cubosome infusion into S. aureus membranes. Using a murine septicemia model, daptomycin-loaded cubosomes significantly reduced the organ bacterial burden of MRSA. Together, these data showed that multifunctional lipid nanocarriers can potentiate the bactericidal activity of daptomycin using a membrane-targeted trojan-horse-like mechanism.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf492","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:13:57Z","timestamp":1761830037000},"page":"e22-e33","source":"Crossref","is-referenced-by-count":2,"title":["Daptomycin-Loaded Nanocarriers Facilitate Synergistic Killing of Methicillin-Resistant\n                    <i>Staphylococcus aureus<\/i>\n                    via Lipid-Mediated Interactions and Targeting"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1543-1634","authenticated-orcid":false,"given":"Jhih-Hang","family":"Jiang","sequence":"first","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University , Clayton, Victoria ,","place":["Australia"]},{"name":"Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University , Melbourne, Victoria ,","place":["Australia"]},{"name":"Centre to Impact AMR, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia Xin","family":"Lim","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute and Department of Biochemistry, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-4415","authenticated-orcid":false,"given":"Xiangfeng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Faculty of Engineering, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-2198","authenticated-orcid":false,"given":"Xenia","family":"Kostoulias","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University , Clayton, Victoria ,","place":["Australia"]},{"name":"Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University , Melbourne, Victoria ,","place":["Australia"]},{"name":"Centre to Impact AMR, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9021-0452","authenticated-orcid":false,"given":"Faye C","family":"Morris","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University , Clayton, Victoria ,","place":["Australia"]},{"name":"Centre to Impact AMR, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-6985","authenticated-orcid":false,"given":"Anton P","family":"Le Brun","sequence":"additional","affiliation":[{"name":"Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation , Kirrawee DC, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-2785","authenticated-orcid":false,"given":"Chun-Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"National Synchrotron Radiation Research Center, Hsinchu Science Park , Hsinchu ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4665-1306","authenticated-orcid":false,"given":"Nageshwar R","family":"Yepuri","sequence":"additional","affiliation":[{"name":"National Deuteration Facility, Australian Nuclear Science and Technology Organisation , Kirrawee DC, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-4370","authenticated-orcid":false,"given":"Hsin-Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute and Department of Biochemistry, Monash University , Clayton, Victoria ,","place":["Australia"]},{"name":"Department of Materials Science and Engineering, Faculty of Engineering, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-2126","authenticated-orcid":false,"given":"Anton Y","family":"Peleg","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University , Clayton, Victoria ,","place":["Australia"]},{"name":"Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University , Melbourne, Victoria ,","place":["Australia"]},{"name":"Centre to Impact AMR, Monash University , Clayton, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"2026031304521430800_jiaf492-B1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrmicro1839","article-title":"Membrane lipid homeostasis in bacteria","volume":"6","author":"Zhang","year":"2008","journal-title":"Nat Rev Microbiol"},{"key":"2026031304521430800_jiaf492-B2","doi-asserted-by":"crossref","first-page":"001048","DOI":"10.1099\/mic.0.001048","article-title":"Streptococcus pneumoniae, S. pyogenes and S. agalactiae membrane phospholipid remodelling in response to human serum","volume":"167","author":"Joyce","year":"2021","journal-title":"Microbiology (Reading)"},{"key":"2026031304521430800_jiaf492-B3","first-page":"47","article-title":"Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections","volume":"9","author":"Gonzalez-Ruiz","year":"2016","journal-title":"Infect Drug Resist"},{"key":"2026031304521430800_jiaf492-B4","doi-asserted-by":"crossref","first-page":"001136","DOI":"10.1099\/mic.0.001136","article-title":"Polymyxin and lipopeptide antibiotics: membrane-targeting drugs of last resort","volume":"168","author":"Ledger","year":"2022","journal-title":"Microbiology (Reading)"},{"key":"2026031304521430800_jiaf492-B5","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1128\/AAC.47.8.2538-2544.2003","article-title":"Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus","volume":"47","author":"Silverman","year":"2003","journal-title":"Antimicrob Agents 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