{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:42:57Z","timestamp":1788374577731,"version":"build-2803163510"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vietnam Ministry of National Defence","award":["2022.75.50"],"award-info":[{"award-number":["2022.75.50"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>As listed by the WHO, the emergence of antibiotic-resistant pathogens, particularly <jats:italic><jats:italic>Staphylococcus aureus<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>Pseudomonas aeruginosa<\/jats:italic><\/jats:italic>, highlights the urgent need for novel antimicrobial agents. In parallel, fungal infections, especially those caused by Candida albicans, have also become increasingly prevalent and clinically challenging, further emphasizing the necessity for broad-spectrum therapeutic strategies. In particular, skin and soft tissue infections (SSTIs) caused by these bacteria and fungal are common in humans and can lead to severe complications if left untreated. Antimicrobial peptides (AMPs) have gained significant attention due to their broad-spectrum antimicrobial activity and immunomodulatory effects. Indolicidin, a naturally occurring cationic AMP, has demonstrated potent antibacterial and antifungal properties. In this study, we designed and synthesized a novel Indolicidin-derivative peptide <jats:bold>IND-4,11K<\/jats:bold> to enhance their antimicrobial activity and stability. The peptide was evaluated <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic> for their antimicrobial efficacy against Gram-positive, Gram-negative bacteria and <jats:italic><jats:italic>Candida albicans<\/jats:italic><\/jats:italic>. <jats:bold>IND-4,11K<\/jats:bold> was then prepared in 0\u20132% cream formula for <jats:italic><jats:italic>in vivo<\/jats:italic><\/jats:italic> testing in rabbit models. These findings suggest that modified Indolicidin-derivatives have potential as novel dual-action antimicrobial agents for treating resistant skin infections and warrant further preclinical investigations.<\/jats:p>","DOI":"10.1371\/journal.pone.0331796","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:23:17Z","timestamp":1757092997000},"page":"e0331796","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Indolicidin derivatives as potent dual-action antifungal and antibacterial agents for the treatment of skin infections: A comprehensive study from in vitro to in vivo evaluation"],"prefix":"10.1371","volume":"20","author":[{"given":"Hoa","family":"Ngo Van","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4815-006X","authenticated-orcid":true,"given":"Huy","family":"Luong Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Le Viet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai Bui Thi","family":"Phuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Do Hai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Quoc","family":"Thang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-203X","authenticated-orcid":true,"given":"Tung","family":"Truong Thanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thinh Vo","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triet Nguyen","family":"Minh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh Nguyen","family":"Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Ngo Thu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Can Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"pone.0331796.ref001","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1007\/s00018-011-0712-8","article-title":"Protecting the boundary: the sentinel role of host defense peptides in the skin","volume":"68","author":"JJ Bernard","year":"2011","journal-title":"Cellular and Molecular Life Sciences"},{"key":"pone.0331796.ref002","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics","volume":"22","author":"RM William","year":"2024","journal-title":"Nature Reviews Microbiology"},{"issue":"1","key":"pone.0331796.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/595011","article-title":"Bad bugs, no drugs: no ESKAPE! 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Jumper","year":"2021","journal-title":"Nature"},{"issue":"43","key":"pone.0331796.ref024","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and Dynamics of the TIP3P, SPC, and SPC\/E Water Models at 298 K","volume":"105","author":"P Mark","year":"2001","journal-title":"J Phys Chem A"},{"issue":"12","key":"pone.0331796.ref025","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: a linear constraint solver for molecular simulations","volume":"18","author":"B Hess","year":"1997","journal-title":"Journal of Computational Chemistry"},{"issue":"12","key":"pone.0331796.ref026","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5 log (N) method for Ewald sums in large systems","volume":"98","author":"T Darden","year":"1993","journal-title":"The Journal of Chemical 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Sciences"},{"issue":"1","key":"pone.0331796.ref030","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1128\/aem.61.1.187-193.1995","article-title":"Relationship between glycocalyx and povidone-iodine resistance in Pseudomonas aeruginosa (ATCC 27853) biofilms","volume":"61","author":"ML Brown","year":"1995","journal-title":"Appl Environ Microbiol"},{"issue":"5","key":"pone.0331796.ref031","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1046\/j.1365-2672.2000.01017.x","article-title":"Susceptibility testing: accurate and reproducible minimum inhibitory concentration (MIC) and non-inhibitory concentration (NIC) values","volume":"88","author":"RJ Lambert","year":"2000","journal-title":"J Appl Microbiol"},{"key":"pone.0331796.ref032","doi-asserted-by":"crossref","first-page":"281","DOI":"10.22270\/jddt.v10i5-s.4430","article-title":"Creams: A review on classification, preparation methods, evaluation and its applications","volume":"10","author":"C Lalita","year":"2020","journal-title":"JDDT"},{"key":"pone.0331796.ref033","first-page":"30","article-title":"Emulsions and emulsifiers","volume":"8","author":"N Sarathchandraprakash","year":"2013","journal-title":"Asian J Exp Chem"},{"issue":"2","key":"pone.0331796.ref034","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02716-21","article-title":"Toward Optimization of a Rabbit Model of Staphylococcus aureus (USA300) Skin and Soft Tissue Infection","volume":"10","author":"N Malachowa","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"5","key":"pone.0331796.ref035","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/ICL.0000000000000689","article-title":"Rabbit Fungal Keratitis Model of Fusarium solani Tested Against Three Commercially Available Antifungal Drugs","volume":"46","author":"TT Aung","year":"2020","journal-title":"Eye Contact Lens"},{"issue":"2020","key":"pone.0331796.ref036","first-page":"113590","article-title":"Skin tissue sample collection, sample homogenization, and analyte extraction strategies for liquid chromatographic mass spectrometry quantification of pharmaceutical compounds","volume":"191","year":"2020","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"9","key":"pone.0331796.ref037","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1038\/s41379-021-00825-7","article-title":"Counting mitoses: SI (ze) matters!","volume":"34","author":"IA Cree","year":"2021","journal-title":"Modern Pathology"},{"issue":"6","key":"pone.0331796.ref038","article-title":"Development of the Bristol Rabbit Pain Scale (BRPS): A multidimensional composite pain scale specific to rabbits (Oryctolagus cuniculus)","volume":"16","author":"B Livia","year":"2021","journal-title":"PLoS One"},{"key":"pone.0331796.ref039","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/laban0607-43","article-title":"Use of behavior analysis to recognize pain in small mammals","volume":"36","author":"M J\u00f6rg","year":"2007","journal-title":"Lab Animal"},{"key":"pone.0331796.ref040","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/026119290503301s12","article-title":"3.6. Subacute and subchronic toxicity","volume":"33","author":"P Prieto","year":"2005","journal-title":"Alternatives to Laboratory Animals"},{"key":"pone.0331796.ref041","author":"A T\u00fcrkyilmaz","year":"2019","journal-title":"Topical pharmaceutical compositions of luliconazole. WIPO (PCT)"},{"issue":"26","key":"pone.0331796.ref042","doi-asserted-by":"crossref","first-page":"24015","DOI":"10.1074\/jbc.M009691200","article-title":"Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria","volume":"276","author":"CL Friedrich","year":"2001","journal-title":"J Biol Chem"},{"issue":"38","key":"pone.0331796.ref043","doi-asserted-by":"crossref","first-page":"12313","DOI":"10.1021\/bi9907936","article-title":"CD spectra of indolicidin antimicrobial peptides suggest turns, not polyproline helix","volume":"38","author":"AS Ladokhin","year":"1999","journal-title":"Biochemistry"},{"issue":"8","key":"pone.0331796.ref044","doi-asserted-by":"crossref","DOI":"10.1016\/j.jid.2020.04.012","article-title":"Research Techniques Made Simple: Mouse Bacterial Skin Infection Models for Immunity Research","volume":"140","author":"C Youn","year":"2020","journal-title":"J Invest Dermatol"},{"issue":"2","key":"pone.0331796.ref045","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00281-011-0292-6","article-title":"Innate and adaptive immune responses against Staphylococcus aureus skin infections","volume":"34","author":"S Krishna","year":"2012","journal-title":"Semin Immunopathol"},{"key":"pone.0331796.ref046","doi-asserted-by":"crossref","first-page":"115839","DOI":"10.1016\/j.carbpol.2020.115839","article-title":"Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review","volume":"233","author":"A Moeini","year":"2020","journal-title":"Carbohydr Polym"},{"issue":"12","key":"pone.0331796.ref047","doi-asserted-by":"crossref","DOI":"10.1002\/jobm.202400510","article-title":"Polysaccharides and Peptides With Wound Healing Activity From Bacteria and Fungi","volume":"64","author":"NP Arslan","year":"2024","journal-title":"J Basic Microbiol"},{"issue":"6","key":"pone.0331796.ref048","first-page":"661","article-title":"Recent trends on wound management: New therapeutic choices based on polymeric carriers","volume":"15","author":"ME Okur","year":"2020","journal-title":"Asian J Pharm Sci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331796","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:23:34Z","timestamp":1757093014000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331796"}},"subtitle":[],"editor":[{"given":"Kamal Ahmad","family":"Qureshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331796","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]}}}