{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:24:18Z","timestamp":1787293458253,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) wound infections remain a major clinical challenge due to antibiotic resistance and biofilm persistence. Although phage therapy has re-emerged as a promising alternative, its efficacy is limited by poor stratum corneum penetration following conventional topical application. Here, we isolated and characterized a lytic MRSA phage, Pelagios, and evaluated its transdermal delivery using detachable dissolvable microneedles (DDMNs). Genomic analyses classified Pelagios within the genus\n                    <jats:italic>Silviavirus<\/jats:italic>\n                    of the family Herelleviridae and indicated that it may represent a novel species. The phage displayed rapid adsorption (\u223c15 min), a short latent period (\u223c20 min), a burst size of \u223c102 PFU\/cell, and stability across physiologically relevant temperature (4 \u00b0C \u201345 \u00b0C) and pH conditions (pH 4\u201310). Whole-genome sequencing confirmed the absence of toxin genes, virulence factors, antimicrobial resistance determinants, and lysogeny-associated genes, supporting its genomic safety. Pelagios exhibited broad lytic activity against multiple clinical MRSA isolates and significantly reduced planktonic bacterial populations both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in\n                    <jats:italic>ex vivo<\/jats:italic>\n                    porcine skin models in a dose-independent manner. It also effectively inhibited MRSA biofilm formation, although eradication of established biofilms was limited. Phage-loaded DDMNs fabricated from hyaluronic acid and gelatin achieved efficient skin penetration, rapid dissolution, complete needle detachment, and markedly improved phage stability at 4 \u00b0C. In\n                    <jats:italic>ex vivo<\/jats:italic>\n                    infection models, DDMN-mediated delivery significantly enhanced antibacterial and biofilm-eradicating efficacy compared with free phage suspension. These findings demonstrate that Pelagios delivered via DDMNs constitutes a safe and effective strategy for treating MRSA-associated wound and biofilm infections.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1928352","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:29Z","timestamp":1787290649000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Detachable dissolving microneedles loaded with Silviavirus phage Pelagios enhance antibacterial efficacy against methicillin resistant Staphylococcus aureus in ex vivo porcine skin"],"prefix":"10.3389","volume":"17","author":[{"given":"Anirut","family":"Yuttagat","sequence":"first","affiliation":[{"name":"Division of Biological Science, Faculty of Science, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Songloilib","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Faculty of Science, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arrita","family":"Rueangrit","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talinee","family":"Chuesanga","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalitwadee","family":"Chotuk","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komwit","family":"Surachat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]},{"name":"Translational Medicine Research Center, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattanaruji","family":"Pomwised","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Faculty of Science, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekachai","family":"Dumkliang","sequence":"additional","affiliation":[{"name":"Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ampapan","family":"Naknaen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University","place":["Hat Yai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6694","DOI":"10.1128\/AEM.01789-14","article-title":"Combined use of bacteriophage k and a novel bacteriophage to reduce Staphylococcus aureus biofilm formation.","volume":"80","author":"Alves","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/s40123-025-01113-2","article-title":"In Vitro activity of bacteriophages against ocular methicillin-resistant S. aureus isolates collected in the US.","volume":"14","author":"Andr\u00e9","year":"2025","journal-title":"Ophthalmol. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1093\/jbcr\/irab175","article-title":"The role of phage therapy in burn wound infections management: Advantages and pitfalls.","volume":"43","author":"Azevedo","year":"2022","journal-title":"J. Burn Care Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/iwj.12049","article-title":"Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: Some remarks about wound infection.","volume":"12","author":"Bessa","year":"2015","journal-title":"Intern. Wound J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1021\/acs.molpharmaceut.4c01058","article-title":"In Vitro drug release and Ex Vivo dermal drug permeation studies of selected commercial benzoyl peroxide topical formulations: Correlation between human and porcine skin models.","volume":"22","author":"Brighenti","year":"2025","journal-title":"Mol. Pharmaceut."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1607210","DOI":"10.3389\/fphar.2025.1607210","article-title":"Advances in clinical applications of microneedle.","volume":"16","author":"Chen","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"106527","DOI":"10.1016\/j.jddst.2024.106527","article-title":"Detachable dissolvable microneedles maintain the viability of phage cocktail and effectively disrupt Pseudomonas aeruginosa biofilm.","volume":"104","author":"Efendi","year":"2025","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1007\/s11095-006-9011-8","article-title":"Pig ear skin ex Vivo as a model for in Vivo Dermatopharmacokinetic studies in man.","volume":"23","author":"Herkenne","year":"2006","journal-title":"Pharm. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"542","DOI":"10.3390\/jcm9020542","article-title":"Progress in microneedle-mediated protein delivery.","volume":"9","author":"Jamaledin","year":"","journal-title":"JCM"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2002129","DOI":"10.1002\/adma.202002129","article-title":"Advances in antimicrobial microneedle patches for combating infections.","volume":"32","author":"Jamaledin","year":"","journal-title":"Adv. Mater."},{"key":"B11","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/j.1524-475X.2007.00321.x","article-title":"Biofilms in chronic wounds.","volume":"16","author":"James","year":"2008","journal-title":"Wound Repair Regenerat."},{"key":"B12","doi-asserted-by":"publisher","first-page":"108252","DOI":"10.1016\/j.jddst.2026.108252","article-title":"Breaking multidrug resistance: Rediscovering phage therapy and delivery strategies.","volume":"120","author":"Javed","year":"2026","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.3389\/fmicb.2019.02949","article-title":"Diversity and function of phage encoded depolymerases.","volume":"10","author":"Knecht","year":"2020","journal-title":"Front. Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.3390\/pharmaceutics14091885","article-title":"Phage therapy against Staphylococcus aureus: Selection and optimization of production protocols of novel broad-spectrum silviavirus phages.","volume":"14","author":"Kolenda","year":"2022","journal-title":"Pharmaceutics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.chom.2019.01.014","article-title":"Phage therapy: A renewed approach to combat antibiotic-resistant bacteria.","volume":"25","author":"Kortright","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-4939-7343-9_3","article-title":"Practical Advice on the One-Step Growth Curve","volume-title":"Bacteriophages","author":"Kropinski","year":"2018"},{"key":"B17","doi-asserted-by":"publisher","first-page":"9251","DOI":"10.1038\/s41598-024-59903-w","article-title":"Isolation and characterisation of a novel Silviavirus bacteriophage promising antimicrobial agent against methicillin-resistant Staphylococcus aureus infections.","volume":"14","author":"Lerdsittikul","year":"2024","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/s41551-018-0337-4","article-title":"Rapidly separable microneedle patch for the sustained release of a contraceptive.","volume":"3","author":"Li","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1267786","DOI":"10.3389\/fmicb.2023.1267786","article-title":"StAP1 phage: An effective tool for treating methicillin-resistant Staphylococcus aureus infections.","volume":"14","author":"Lu","year":"2023","journal-title":"Front. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0044824","DOI":"10.1128\/aac.00448-24","article-title":"Synergy of lytic phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii.","volume":"68","author":"Luo","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3390\/gels10040244","article-title":"Alginate- and chitosan-modified gelatin hydrogel microbeads for delivery of E. coli phages.","volume":"10","author":"Moghtader","year":"2024","journal-title":"Gels"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0400925","DOI":"10.1128\/spectrum.04009-25","article-title":"Synergistic effects of halo-plaque forming phage cocktails against polymicrobial Acinetobacter baumannii and Staphylococcus aureus.","volume":"14","author":"Naknaen","year":"2026","journal-title":"Microbiol. Spectr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"109790","DOI":"10.1016\/j.isci.2024.109790","article-title":"Nucleus-forming jumbophage PhiKZ therapeutically outcompetes non-nucleus-forming jumbophage Callisto.","volume":"27","author":"Naknaen","year":"2024","journal-title":"iScience"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.3390\/molecules23092392","article-title":"Treatment strategies for infected wounds.","volume":"23","author":"Negut","year":"2018","journal-title":"Molecules"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1128\/AEM.71.4.1836-1842.2005","article-title":"Potential of the polyvalent Anti- Staphylococcus bacteriophage K for control of antibiotic-resistant Staphylococci from hospitals.","volume":"71","author":"O\u2019Flaherty","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"100398","DOI":"10.1016\/j.jvacx.2023.100398","article-title":"Detachable-dissolvable-microneedle as a potent subunit vaccine delivery device that requires no cold-chain.","volume":"15","author":"Phoka","year":"2023","journal-title":"Vaccine: X"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.3390\/v15122287","article-title":"Isolation and characterization of new bacteriophages against Staphylococcal clinical isolates from diabetic foot ulcers.","volume":"15","author":"Plumet","year":"2023","journal-title":"Viruses"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1038\/s41591-019-0606-0","article-title":"Microneedle patch drug delivery in the gut.","volume":"25","author":"Prausnitz","year":"2019","journal-title":"Nat. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"103991","DOI":"10.1016\/j.jddst.2022.103991","article-title":"Alginate chitosan microbeads and thermos-responsive hyaluronic acid hydrogel for phage delivery.","volume":"79","author":"Rotman","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"24114","DOI":"10.1038\/s41598-021-03503-5","article-title":"Detachable dissolvable microneedles: Intra-epidermal and intradermal diffusion, effect on skin surface, and application in hyperpigmentation treatment.","volume":"11","author":"Sawutdeechaikul","year":"2021","journal-title":"Sci. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","article-title":"Human skin wounds: A major and snowballing threat to public health and the economy.","volume":"17","author":"Sen","year":"2009","journal-title":"Wound Repair Regenerat."},{"key":"B32","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1586\/14787210.2015.1023291","article-title":"Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus.","volume":"13","author":"Serra","year":"2015","journal-title":"Exp. Rev. Anti-infect. Therapy"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2309622","DOI":"10.1002\/advs.202309622","article-title":"Reactive microneedle patches with antibacterial and dead bacteria-trapping abilities for skin infection treatment.","volume":"11","author":"Shan","year":"2024","journal-title":"Adv. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"964","DOI":"10.3390\/v14050964","article-title":"Antibiofilm efficacy of the Pseudomonas aeruginosa Pbunavirus vB_PaeM-SMS29 loaded onto dissolving polyvinyl alcohol microneedles.","volume":"14","author":"Sillankorva","year":"2022","journal-title":"Viruses"},{"key":"B35","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12866-025-03854-3","article-title":"Characterization of a novel lytic phage vB_AbaM_AB4P2 encoding depolymerase and its application in eliminating biofilms formed by Acinetobacter baumannii.","volume":"25","author":"Su","year":"2025","journal-title":"BMC Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/wrr.13164","article-title":"MRSA infection, re-infection and clinical outcomes in diabetic foot infections.","volume":"32","author":"Suludere","year":"2024","journal-title":"Wound Repair Regenerat."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3304","DOI":"10.1002\/jps.20980","article-title":"Stabilization of proteins by recombinant human gelatins.","volume":"96","author":"Thyagarajapuram","year":"2007","journal-title":"J. Pharmaceut. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s00705-022-05694-2","article-title":"Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee.","volume":"168","author":"Turner","year":"2023","journal-title":"Arch. Virol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/s41579-024-01035-z","article-title":"The wound microbiota: Microbial mechanisms of impaired wound healing and infection.","volume":"22","author":"Uberoi","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1089\/wound.2012.0381","article-title":"Biofilms and inflammation in chronic wounds.","volume":"2","author":"Zhao","year":"2013","journal-title":"Adv. Wound Care"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1928352\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:30Z","timestamp":1787290650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1928352\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":40,"alternative-id":["10.3389\/fmicb.2026.1928352"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1928352","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1928352"}}