{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:37:08Z","timestamp":1792773428919,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["408564\/2023-7"],"award-info":[{"award-number":["408564\/2023-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["408678\/2024-0"],"award-info":[{"award-number":["408678\/2024-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["303211\/2024-5"],"award-info":[{"award-number":["303211\/2024-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","award":["APQ-03498-22"],"award-info":[{"award-number":["APQ-03498-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"publisher","award":["E-26\/211.284\/2021"],"award-info":[{"award-number":["E-26\/211.284\/2021"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic wound infections are frequently associated with biofilm-forming pathogens that impair healing and reduce the effectiveness of antimicrobial therapies. This study evaluated the antimicrobial, antibiofilm, synergistic, and antivirulence activities of two indole alkaloids, 3-(1H-indol-3-yl)propanoic acid (C1) and 1H-indole-2-carboxylic acid (C2), and investigated their incorporation into chitosan-based biodressings for infected wound management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Antimicrobial activity was evaluated by agar diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), biofilm inhibition, and checkerboard assays. Cytotoxicity was assessed using RAW 264.7 macrophages and HaCaT keratinocytes. Biodressings were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis, porosity, and release kinetics, while antimicrobial activity and gene expression were evaluated by agar diffusion and reverse transcription quantitative PCR. Both compounds exhibited broad-spectrum antibacterial activity, particularly against Staphylococcus aureus and Staphylococcus epidermidis, inhibited biofilm formation at sub-MIC concentrations, and showed synergistic or additive interactions with conventional antibiotics. The alkaloids displayed low cytotoxicity and were successfully incorporated into chitosan matrices, showing a biphasic release profile over the evaluated period while preserving antimicrobial activity. Functionalized biodressings significantly downregulated genes involved in adhesion (fimH), biofilm formation (icaA, icaD, aap, and pslA), quorum sensing (lasR), and virulence regulation (sarA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Indole alkaloid-loaded chitosan biodressings constitute a promising multifunctional platform that combines antibacterial, antibiofilm, antibiotic-potentiating, and antivirulence activities while maintaining favorable cytocompatibility. These findings support further investigation of indole alkaloid-loaded chitosan biodressings as a potential biomaterial-based strategy for managing wound-associated bacterial infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxag246","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:51:21Z","timestamp":1790855481000},"source":"Crossref","is-referenced-by-count":0,"title":["Bioactive chitosan dressings functionalized with indole alkaloids suppress biofilm development and virulence traits in bacterial species relevant to wound infections"],"prefix":"10.1093","volume":"137","author":[{"given":"Pedro Henrique","family":"de\u00a0Jesus\u00a0Barbosa","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Vinicius","family":"de\u00a0Sousa\u00a0Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele","family":"de\u00a0Vasconcelos\u00a0Sobreira\u00a0Braathen","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Witallo","family":"Sousa\u00a0do\u00a0Nascimento","sequence":"additional","affiliation":[{"name":"Departamento de Entomologia, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayvson Ayala","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Entomologia, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriete","family":"da\u00a0Silva\u00a0Vieira","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaspar","family":"Diaz-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemmyson Rom\u00e1rio","family":"de\u00a0Jesus","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro C\u00e9sar","family":"Rossi","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Molecular e Celular, Laborat\u00f3rio de Mobiloma e Resist\u00eancia (MoRe), Universidade Federal Fluminense , Niter\u00f3i, Rio de Janeiro 24210-201 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa Alves Nogueira","family":"Diaz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa, Minas Gerais 36570-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026102311073173500_bib1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3934\/microbiol.2023017","article-title":"Comparative in vitro activity of various antibiotic against planktonic and biofilm and the gene expression profile in Pseudomonas aeruginosa","volume":"9","author":"Abu-Sini","year":"2023","journal-title":"AIMSMICRO"},{"key":"2026102311073173500_bib2","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3390\/ph17060749","article-title":"Design and characterization of chitosan-based smart injectable hydrogel for improved sustained release of antinarcotics","volume":"17","author":"Aftab","year":"2024","journal-title":"Pharmaceuticals"},{"key":"2026102311073173500_bib3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.24996\/ijs.2020.61.2.6","article-title":"Gene Expression of pelA and pslA in Pseudomonas aeruginosa under Gentamicin Stress","author":"AL-Sheikhly","year":"2020","journal-title":"eijs"},{"key":"2026102311073173500_bib4","doi-asserted-by":"publisher","first-page":"11365","DOI":"10.3390\/ijms262311365","article-title":"Wounds and the microbiota: the healing interplay between host and microbial communities","volume":"26","author":"Al-Taweel","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026102311073173500_bib5","doi-asserted-by":"publisher","first-page":"101543","DOI":"10.1016\/j.mex.2021.101543","article-title":"New and simplified method for drug combination studies by checkerboard assay","volume":"8","author":"Bellio","year":"2021","journal-title":"MethodsX"},{"key":"2026102311073173500_bib6","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1002\/jps.21210","article-title":"Wound healing dressings and drug delivery systems: a review","volume":"97","author":"Boateng","year":"2008","journal-title":"J Pharm Sci"},{"key":"2026102311073173500_bib7","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.femsre.2003.09.003","article-title":"Regulation of virulence determinants in Staphylococcus aureus\u202f: complexity and applications","volume":"28","author":"Bronner","year":"2004","journal-title":"FEMS Microbiol Rev"},{"key":"2026102311073173500_bib8","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1016\/j.ajic.2012.08.008","article-title":"Methicillin-resistant Staphylococcus aureus in Rio de Janeiro hospitals: dissemination of the USA400\/ST1 and USA800\/ST5 SCCmec type IV and USA100\/ST5 SCCmec type II lineages in a public institution and polyclonal presence in a private one","volume":"41","author":"Caboclo","year":"2013","journal-title":"Am J Infect Control"},{"key":"2026102311073173500_bib9","author":"CLSI","year":"2025"},{"key":"2026102311073173500_bib10","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1586\/eri.11.59","article-title":"Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects","volume":"9","author":"Dai","year":"2011","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2026102311073173500_bib11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.mtchem.2018.05.001","article-title":"Role of plant alkaloids on human health: a review of biological activities","volume":"9","author":"Debnath","year":"2018","journal-title":"Mater Today Chem"},{"key":"2026102311073173500_bib12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.7603\/s40681-015-0022-9","article-title":"Wound dressings\u2014a review","volume":"5","author":"Dhivya","year":"2015","journal-title":"BioMed"},{"key":"2026102311073173500_bib13","doi-asserted-by":"publisher","first-page":"e70371","DOI":"10.1111\/1758-2229.70371","article-title":"Modulation of quorum sensing and virulence gene expression in Escherichia coli by extracts of Physalis alkekengi","volume":"18","author":"Doolaby","year":"2026","journal-title":"Environ Microbiol Rep"},{"key":"2026102311073173500_bib14","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nrmicro.2016.94","article-title":"Biofilms: an emergent form of bacterial life","volume":"14","author":"Flemming","year":"2016","journal-title":"Nat Rev Micro"},{"key":"2026102311073173500_bib15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00284-025-04684-2","article-title":"Natural anti-biofilm agents: a comprehensive review and future perspectives","volume":"83","author":"Jeyachandran","year":"2026","journal-title":"Curr Microbiol"},{"key":"2026102311073173500_bib16","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13568-021-01247-z","article-title":"Down-regulation of biofilm-associated genes in mecA-positive methicillin-resistant S. aureus treated with M. communis extract and its antibacterial activity","volume":"11","author":"Khaleghi","year":"2021","journal-title":"AMB Expr"},{"key":"2026102311073173500_bib17","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s12257-008-0188-z","article-title":"Characterization of LasR protein involved in bacterial quorum sensing mechanism of Pseudomonas aeruginosa","volume":"14","author":"Liu","year":"2009","journal-title":"Biotechnol Bioproc E"},{"key":"2026102311073173500_bib18","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.3390\/bioengineering12111178","article-title":"Smart biomaterials in wound healing: advances, challenges, and future directions in intelligent dressing design","volume":"12","author":"Liu","year":"2025","journal-title":"Bioeng"},{"key":"2026102311073173500_bib19","doi-asserted-by":"publisher","first-page":"20","DOI":"10.12968\/jowc.2017.26.1.20","article-title":"the prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data","volume":"26","author":"Malone","year":"2017","journal-title":"J Wound Care"},{"key":"2026102311073173500_bib20","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.3390\/pharmaceutics15061606","article-title":"Antimicrobial biomaterials for chronic wound care","volume":"15","author":"Miron","year":"2023","journal-title":"Pharmaceutics"},{"key":"2026102311073173500_bib21","doi-asserted-by":"publisher","first-page":"e65321","DOI":"10.5812\/archcid.65321","article-title":"Evaluation of antibacterial activity of Zataria multiflora against the expression of icaADB and aap Gene and biofilm formation in Staphylococcus epidermidis","volume":"In Press","author":"Mottaghiyan","year":"2019","journal-title":"Arch Clin Infect Dis"},{"key":"2026102311073173500_bib22","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fphar.2025.1577331","article-title":"Escitalopram oxalate-loaded chitosan nanoparticle in situ gel formulation intended for direct nose-to-brain delivery: in vitro, ex vivo, and in vivo pharmacokinetic evaluation","volume":"16","author":"Mujtaba","year":"2025","journal-title":"Front Pharmacol"},{"key":"2026102311073173500_bib23","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990\u20132021: a systematic analysis with forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"2026102311073173500_bib24","doi-asserted-by":"publisher","first-page":"13233","DOI":"10.1111\/wrr.13233","article-title":"Recent advances in bioactive wound dressings","volume":"33","author":"Nur","year":"2025","journal-title":"Wound Repair Regen"},{"key":"2026102311073173500_bib25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/9048245","article-title":"Multidrug-resistant biofilm, quorum sensing, quorum quenching, and antibacterial activities of indole derivatives as potential eradication approaches","volume":"2022","author":"Odularu","year":"2022","journal-title":"Biomed Res Int"},{"key":"2026102311073173500_bib26","doi-asserted-by":"publisher","first-page":"9048245","DOI":"10.1155\/2022\/9048245","article-title":"Multidrug-resistant biofilm, quorum sensing, quorum quenching, and antibacterial activities of indole derivatives as potential eradication approaches","volume":"2022","author":"Odularu","year":"2022","journal-title":"Biomed Res Int"},{"key":"2026102311073173500_bib27","doi-asserted-by":"publisher","first-page":"251","DOI":"10.20473\/fmi.v55i4.17311","article-title":"The correlation between icaA and icaD genes with biofilm formation Staphylococcus epidermidis in vitro","volume":"55","author":"Rachmawati","year":"2020","journal-title":"FMI"},{"key":"2026102311073173500_bib28","doi-asserted-by":"publisher","first-page":"5235071","DOI":"10.1155\/ijm\/5235071","article-title":"Differential Expression of fimH, ihf, upaB, and upaH Genes in biofilms- and suspension-Grown bacteria from samples of different uropathogenic strains of Escherichia coli","volume":"2024","author":"Rodr\u00edguez-Miranda","year":"2024","journal-title":"Int J Microbiol"},{"key":"2026102311073173500_bib29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41579-022-00780-3","article-title":"Staphylococcus epidermidis and its dual lifestyle in skin health and infection","volume":"21","author":"Severn","year":"2023","journal-title":"Nat Rev Micro"},{"key":"2026102311073173500_bib30","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fcimb.2026.1589866","article-title":"Bacterial biofilm conundrum: insight into the frontiers of antibiotic resistance and state-of-the-art anti-biofilm interventions","volume":"16","author":"Sharma","year":"2026","journal-title":"Front Cell Infect Microbiol"},{"key":"2026102311073173500_bib31","doi-asserted-by":"publisher","first-page":"7784","DOI":"10.3390\/jcm14217784","article-title":"Biofilms and chronic wounds: pathogenesis and treatment options","volume":"14","author":"Shen","year":"2025","journal-title":"JCM"},{"key":"2026102311073173500_bib32","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1007\/s10924-025-03550-3","article-title":"Development of a sustainable smart biodressing using chitosan, albumin, and green propolis for dermal lesion care: an in vitro study with multivariate analysis","volume":"33","author":"Sousa\u00a0de\u00a0Pereira","year":"2025","journal-title":"J Polym Environ"},{"key":"2026102311073173500_bib33","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1111\/j.1600-0463.2007.apm_630.x","article-title":"Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci","volume":"115","author":"Stepanovi\u0107","year":"2007","journal-title":"APMIS"},{"key":"2026102311073173500_bib34","doi-asserted-by":"crossref","first-page":"ovaf046","DOI":"10.1093\/lambio\/ovaf046","article-title":"Hydrocleys nymphoides (water poppy): a cosmopolitan aquatic plant with a phytochemical-rich extract exhibiting antimicrobial and antibiofilm activity against multidrug-resistant Staphylococcus","volume":"78","author":"Toneto\u00a0Francisco","year":"2025","journal-title":"Lett Appl Microbiol"},{"key":"2026102311073173500_bib35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat Rev Micro"},{"key":"2026102311073173500_bib36","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-018-0141-x","article-title":"Drug combinations: a strategy to extend the life of antibiotics in the 21st century","volume":"17","author":"Tyers","year":"2019","journal-title":"Nat Rev Micro"},{"key":"2026102311073173500_bib37","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.aiepr.2023.07.002","article-title":"Chitosan-based nanostructured biomaterials: synthesis, properties, and biomedical applications","volume":"7","author":"Ul-Islam","year":"2024","journal-title":"Adv Ind Eng Polym Res"},{"key":"2026102311073173500_bib38","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1039\/D3MD00677H","article-title":"Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies","volume":"15","author":"Zeng","year":"2024","journal-title":"RSC Med Chem"},{"key":"2026102311073173500_bib39","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.3390\/molecules31071204","article-title":"Natural alkaloids as antimicrobial agents: mechanisms, potentials and challenges","volume":"31","author":"Zhang","year":"2026","journal-title":"Molecules"}],"container-title":["Journal of Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jambio\/advance-article-pdf\/doi\/10.1093\/jambio\/lxag246\/71559843\/lxag246.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/10\/lxag246\/71559843\/lxag246.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/10\/lxag246\/71559843\/lxag246.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T15:07:40Z","timestamp":1792768060000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jambio\/article\/doi\/10.1093\/jambio\/lxag246\/8859080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jambio\/lxag246","relation":{},"ISSN":["1365-2672"],"issn-type":[{"value":"1365-2672","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,10,1]]},"article-number":"lxag246"}}