{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:13:05Z","timestamp":1791072785554,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM109259"],"award-info":[{"award-number":["GM109259"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI130554"],"award-info":[{"award-number":["AI130554"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM110444"],"award-info":[{"award-number":["GM110444"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000153","name":"Division of Biological Infrastructure","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000153","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2019.01348","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T06:01:06Z","timestamp":1561096866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Hydrogels Embedded With Melittin and Tobramycin Are Effective Against Pseudomonas aeruginosa Biofilms in an Animal Wound Model"],"prefix":"10.3389","volume":"10","author":[{"given":"Michael M.","family":"Maiden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell P.","family":"Zachos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S24","DOI":"10.12968\/jowc.2017.26.Sup7.S24","article-title":"A bioluminescent Pseudomonas aeruginosa wound model reveals increased mortality of type 1 diabetic mice to biofilm infection.","volume":"26","author":"Agostinho Hunt","year":"2017","journal-title":"J. Wound Care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1007\/s00726-018-2596-5","article-title":"Action mechanism of melittin-derived antimicrobial peptides, MDP1 and MDP2, de novo designed against multidrug resistant bacteria.","volume":"50","author":"Akbari","year":"2018","journal-title":"Amino Acids"},{"key":"B3","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.burns.2004.03.005","article-title":"The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients.","volume":"30","author":"Altoparlak","year":"2004","journal-title":"Burns"},{"key":"B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/jac\/48.suppl_1.5","article-title":"Determination of minimum inhibitory concentrations.","volume":"48","author":"Andrews","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1128\/JB.01000-07","article-title":"Genome sequence of Staphylococcus aureus strain newman and comparative analysis of Staphylococcal genomes: polymorphism and evolution of two major pathogenicity islands.","volume":"190","author":"Baba","year":"2007","journal-title":"J. Bacteriol."},{"key":"B6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2165\/00003495-200161060-00001","article-title":"Aminoglycoside adaptive resistance: importance for effective dosage regimens.","volume":"61","author":"Barclay","year":"2001","journal-title":"Drugs"},{"key":"B7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s10096-018-3189-7","article-title":"Highly synergistic activity of melittin with imipenem and colistin in biofilm inhibition against multidrug-resistant strong biofilm producer strains of Acinetobacter baumannii.","volume":"37","author":"Bardbari","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.ijbiomac.2013.04.073","article-title":"Chitosan\/alginate crosslinked hydrogels: preparation, characterization and application for cell growth purposes.","volume":"59","author":"Baysal","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature17042","article-title":"Antibacterial drug discovery in the resistance era.","volume":"529","author":"Brown","year":"2016","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009779","article-title":"Antibiotic and anti-inflammatory therapies for cystic fibrosis.","volume":"3","author":"Chmiel","year":"2013","journal-title":"Cold Spring Harbor Perspect. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6483","DOI":"10.3892\/mmr.2015.4275","article-title":"Melittin, a honeybee venom-derived antimicrobial peptide, may target methicillin-resistant Staphylococcus aureus.","volume":"12","author":"Choi","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1093\/glycob\/cww011","article-title":"N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3.","volume":"26","author":"Craciun","year":"2016","journal-title":"Glycobiology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1128\/aac.38.11.2590","article-title":"Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus.","volume":"38","author":"de Lencastre","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1002\/mbo3.141","article-title":"Developing an international Pseudomonas aeruginosa reference panel.","volume":"2","author":"De Soyza","year":"2013","journal-title":"Microbiologyopen"},{"key":"B15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1128\/CMR.15.2.167-193.2002","article-title":"Biofilms: survival mechanisms of clinically relevant microorganisms.","volume":"15","author":"Donlan","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.peptides.2014.09.021","article-title":"Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides.","volume":"62","author":"Dosler","year":"2014","journal-title":"Peptides"},{"key":"B17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1179\/1973947815Y.0000000004","article-title":"Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria.","volume":"28","author":"Dosler","year":"2016","journal-title":"J. Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.peptides.2013.08.008","article-title":"In vitro pharmacokinetics of antimicrobial cationic peptides alone and in combination with antibiotics against methicillin resistant Staphylococcus aureus biofilms.","volume":"49","author":"Dosler","year":"2013","journal-title":"Peptides"},{"key":"B19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/ppul.10127","article-title":"Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis.","volume":"34","author":"Emerson","year":"2002","journal-title":"Pediatr. Pulmonol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1086\/429323","article-title":"Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections.","volume":"40","author":"Falagas","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e537","DOI":"10.1128\/mBio.00537-12","article-title":"A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes.","volume":"4","author":"Fey","year":"2012","journal-title":"mBio"},{"key":"B22","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1089\/wound.2015.0635","article-title":"Challenges in the treatment of chronic wounds.","volume":"4","author":"Frykberg","year":"2015","journal-title":"Adv. Wound Care"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(82)90471-8","article-title":"Nephrotoxicity of aminoglycosides.","volume":"320","author":"Gabriel","year":"1982","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/4012394","article-title":"Melittin inhibition and eradication activity for resistant polymicrobial biofilm isolated from a dairy industry after disinfection.","volume":"2019","author":"Galdiero","year":"2019","journal-title":"Int. J. Microbiol."},{"key":"B25","author":"Gilbert","year":"2013","journal-title":"The Sanford Guide to Antimicrobial Therapy."},{"key":"B26","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1099\/00222615-29-1-41","article-title":"Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa.","volume":"29","author":"Gilleland","year":"1989","journal-title":"J. Med. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1038\/nbt1267","article-title":"Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.","volume":"24","author":"Hancock","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jcf.2005.05.005","article-title":"Infection and inflammation in cystic fibrosis: a short review.","volume":"4","author":"Heijerman","year":"2005","journal-title":"J. Cystic Fibrosis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1086\/656788","article-title":"Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa.","volume":"202","author":"Herrmann","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1099\/00221287-13-3-572","article-title":"Genetic recombination in Pseudomonas aeruginosa.","volume":"13","author":"Holloway","year":"1955","journal-title":"J. Gen. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3791\/55991","article-title":"Come to the light side: in vivo monitoring of pseudomonas aeruginosa biofilm infections in chronic wounds in a diabetic hairless murine model.","volume":"128","author":"Hunt","year":"2017","journal-title":"JoVE"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21050616","article-title":"Anti-inflammatory applications of melittin, a major component of bee venom: detailed mechanism of action and adverse effects.","volume":"21","author":"Lee","year":"2016","journal-title":"Molecules"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1021\/ja0495359","article-title":"Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides.","volume":"126","author":"Lee","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1038\/jid.2014.75","article-title":"The protective effects of melittin on Propionibacterium acnes \u2013induced inflammatory responses in vitro and in vivo.","volume":"134","author":"Lee","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1128\/AAC.45.4.999-1007.2001","article-title":"Riddle of biofilm resistance.","volume":"45","author":"Lewis","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/jbm.a.33045","article-title":"Superabsorbent polysaccharide hydrogels based on pullulan derivate as antibacterial release wound dressing.","author":"Li","year":"2011","journal-title":"J. Biomed. Mater. Res."},{"key":"B37","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/jac\/5.5.613","article-title":"Paradoxical effect of aminoglycoside antibiotics on the growth of Gram-negative bacilli.","volume":"5","author":"Lorian","year":"1979","journal-title":"J. Antimicrob. Chemother."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00146-18","article-title":"Triclosan is an aminoglycoside adjuvant for eradication of Pseudomonas aeruginosa biofilms.","volume":"62","author":"Maiden","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"B39","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1093\/jac\/dky545","article-title":"The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential.","volume":"74","author":"Maiden","year":"","journal-title":"J. Antimicrob. Chemother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/nrmicro2095","article-title":"Antimicrobial peptides: linking partition, activity and high membrane-bound concentrations.","volume":"7","author":"Melo","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"6191","DOI":"10.1128\/JB.01651-09","article-title":"Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis.","volume":"192","author":"Mulcahy","year":"2010","journal-title":"J. Bacteriol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/microorganisms5010009","article-title":"Microbial biofilms and chronic wounds.","volume":"5","author":"Omar","year":"2017","journal-title":"Microorganisms"},{"key":"B43","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/s0734-9750(03)00077-6","article-title":"Ribosomally synthesized peptides with antimicrobial properties: biosynthesis, structure, function, and applications.","volume":"21","author":"Papagianni","year":"2003","journal-title":"Biotechnol. Adv."},{"key":"B44","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.micpath.2018.11.055","article-title":"Single dose eradication of extensively drug resistant Acinetobacter spp. in a mouse model of burn infection by melittin antimicrobial peptide.","volume":"127","author":"Pashaei","year":"2019","journal-title":"Microbial Pathog."},{"key":"B45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.micpath.2017.09.046","article-title":"Melittin and its potential in the destruction and inhibition of the biofilm formation by Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.","volume":"112","author":"Picoli","year":"2017","journal-title":"Microbial Pathog."},{"key":"B46","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s10540-006-9030-z","article-title":"Melittin: a membrane-active peptide with diverse functions.","volume":"27","author":"Raghuraman","year":"2006","journal-title":"Biosci. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"5363","DOI":"10.1128\/AAC.03163-14","article-title":"A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms.","volume":"58","author":"Reffuveille","year":"2014","journal-title":"Antimicrob Agents Chemother."},{"key":"B48","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/bip.22412","article-title":"Antimicrobial hydrogels for the treatment of infection.","volume":"100","author":"Salom\u00e9 Veiga","year":"2013","journal-title":"Biopolymers"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4369","DOI":"10.1128\/AAC.00583-11","article-title":"Identification of a novel benzimidazole that inhibits bacterial biofilm formation in a broad-spectrum manner.","volume":"55","author":"Sambanthamoorthy","year":"2011","journal-title":"Antimicrob Agents Chemother."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2011\/605195","article-title":"Antimicrobial susceptibility patterns of Pseudomonas aeruginosa from diabetes patients with foot ulcers.","volume":"2011","author":"Sivanmaliappan","year":"2011","journal-title":"Int. J. Microbiol."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics6040031","article-title":"Antimicrobial activity of bee venom and melittin against Borrelia burgdorferi.","volume":"6","author":"Socarras","year":"2017","journal-title":"Antibiotics"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.01095-15","article-title":"Draft genome sequence of methicillin-sensitive Staphylococcus aureus ATCC 29213.","volume":"3","author":"Soni","year":"2015","journal-title":"Genome Announc."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1056\/NEJMc1502191","article-title":"Origins of cystic fibrosis lung disease.","volume":"372","author":"Stoltz","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.ijantimicag.2016.09.010","article-title":"Pharmacokinetics\/pharmacodynamics of colistin and polymyxin B: are we there yet?","volume":"48","author":"Tran","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/0471143030.cb1016s47","article-title":"Preparation of hydrogel substrates with tunable mechanical properties.","volume":"47","author":"Tse","year":"2010","journal-title":"Curr. Protocols Cell Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1111\/1462-2920.12155","article-title":"The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin.","volume":"15","author":"Tseng","year":"2013","journal-title":"Environ. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13102818.2017.1332493","article-title":"Feasibility of chitosan-alginate (Chi-Alg) hydrogel used as scaffold for neural tissue engineering: a pilot study in vitro.","volume":"23","author":"Wang","year":"2017","journal-title":"Biotechnol. Biotechnol. Equipment"},{"key":"B58","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1124\/pr.55.1.2","article-title":"Mechanisms of antimicrobial peptide action and resistance.","volume":"55","author":"Yeaman","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122085","article-title":"Inflammation in chronic wounds.","volume":"17","author":"Zhao","year":"2016","journal-title":"IJMS"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2019.01348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T01:45:48Z","timestamp":1569289548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2019.01348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":59,"alternative-id":["10.3389\/fmicb.2019.01348"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2019.01348","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,20]]},"article-number":"1348"}}