{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:43:00Z","timestamp":1785548580506,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465687\/2014-8"],"award-info":[{"award-number":["465687\/2014-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Nanotecnologia Farmac\u00eautica","award":["2014\/50928-2"],"award-info":[{"award-number":["2014\/50928-2"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["23038.000776\/2017O54"],"award-info":[{"award-number":["23038.000776\/2017O54"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 \u00d7 105 cells (4 \u00b5L) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 \u00b5mol\/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 \u00b5mol\/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.<\/jats:p>","DOI":"10.3390\/toxins11040203","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:31:57Z","timestamp":1554377517000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-2487","authenticated-orcid":false,"given":"Carolina Nunes da","family":"Silva","sequence":"first","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-9795","authenticated-orcid":false,"given":"Flavia Rodrigues da","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade-PPGCAS, Universidade Federal de Sergipe, Lagarto 49400-000 SE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5287-455X","authenticated-orcid":false,"given":"Lays Fernanda Nunes","family":"Dourado","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-1015","authenticated-orcid":false,"given":"Pablo Victor Mendes dos","family":"Reis","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rummenigge Oliveira","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-0717","authenticated-orcid":false,"given":"Bruna Lopes da","family":"Costa","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-0178","authenticated-orcid":false,"given":"Paula Santos","family":"Nunes","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade-PPGCAS, Universidade Federal de Sergipe, Lagarto 49400-000 SE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1695-0612","authenticated-orcid":false,"given":"Fl\u00e1vio Almeida","family":"Amaral","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L\u00facia dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"de Lima","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Biomedicina e Medicina, Ensino e Pesquisa da Santa Casa de Belo Horizonte, Grupo Santa Casa de Belo Horizonte, Belo Horizonte 30150-250, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-8936","authenticated-orcid":false,"given":"Armando da","family":"Silva Cunha J\u00fanior","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901 MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"O\u2019Callaghan, R.J. (2018). The Pathogenesis of Staphylococcus aureus Eye Infections. Pathogens, 10.","DOI":"10.3390\/pathogens7010009"},{"key":"ref_2","first-page":"214","article-title":"Corneal blindness: A global perspective","volume":"79","author":"Whitcher","year":"2001","journal-title":"Bull. World Health Organ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1055\/s-0035-1545994","article-title":"Bacterial Keratitis","volume":"232","author":"Rachwalik","year":"2015","journal-title":"Klinische Monatsbl\u00e4tter Augenheilkunde"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ophtha.2005.08.013","article-title":"Microbial keratitis predisposing factors and morbidity","volume":"113","author":"Keay","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1442-9071.2006.01164.x","article-title":"Resisting susceptibility: Bacterial keratitis and generations of antibiotics","volume":"34","author":"McGhee","year":"2006","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/vop.12140","article-title":"Mucoadhesive chitosan films as a potential ocular delivery system for ofloxacin: Preliminary in vitro studies","volume":"17","author":"Viana","year":"2014","journal-title":"Vet. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1097\/00003226-200111000-00020","article-title":"Effectiveness of Ciprofloxacin and Ofloxacin in a prophylaxis model of Staphylococcus Keratitis","volume":"20","author":"Dajcs","year":"2001","journal-title":"Cornea"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0924-8579(03)00180-8","article-title":"Antimicrobial peptides in animals and their role in host defences","volume":"22","author":"Brogden","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1586\/14787210.2014.976613","article-title":"Antimicrobial peptides: Therapeutic potentials","volume":"12","author":"Kang","year":"2014","journal-title":"Expert Rev. Ant. Infect. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.peptides.2015.05.012","article-title":"Antimicrobial peptides: Possible anti-infective agents","volume":"72","author":"Lakshmaiah","year":"2015","journal-title":"Peptides"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jfo.2017.12.007","article-title":"Corneal collagen cross-linking to treat infectious keratitis","volume":"41","author":"Atia","year":"2018","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00726-009-0385-x","article-title":"LyeTx I, a potent antimicrobial peptide from the venom of the spider Lycosa erythrognatha","volume":"39","author":"Santos","year":"2010","journal-title":"Amino Acids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1902\/jop.2013.120679","article-title":"Peptides: B-cyclodextrin inclusion compounds as highly effective antimicrobial and anti-epithelial proliferation agents","volume":"84.","author":"Consuegra","year":"2013","journal-title":"J. Periodontol."},{"key":"ref_14","first-page":"88","article-title":"Antibacterial Effect of Synthetic Peptide LyeTxI and LyeTxI\/\u03b2-Cyclodextrin Association Compound Against Planktonic and Multispecies Biofilms of Periodontal Pathogens","volume":"88","author":"Santos","year":"2017","journal-title":"J. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"667","DOI":"10.3389\/fmicb.2018.00667","article-title":"LyeTxI-b, a Synthetic Peptide Derived from Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo","volume":"9","author":"Reis","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40409-018-0168-5","article-title":"Intravitreal injection of the synthetic peptide LyeTx I b, derived of a spider toxin, in rabbit\u2019s eye is safety and prevents neovascularization on Chorio-allantoic Membrane Model","volume":"24","author":"Silva","year":"2018","journal-title":"J. Venom. Anim. Toxins Include. Trop. Dis."},{"key":"ref_17","unstructured":"Habboush, Y., and Guzman, N. (2019, March 03). Antibiotic Resistance. SourceStatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513277\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/wrr.12034","article-title":"Wound biofilms: Lessons learned from oral biofilms","volume":"21","author":"Mancl","year":"2013","journal-title":"Wound Repair Regen"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/exd.12929","article-title":"Antimicrobial peptides and wound healing: Biological and therapeutic considerations","volume":"25","author":"Mangoni","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.12968\/jowc.2010.19.2.46966","article-title":"Chronic wounds and the medical biofilm paradigm","volume":"19","author":"Wolcott","year":"2010","journal-title":"J. Wound Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.tim.2011.04.005","article-title":"Pseudomonas aeruginosa: All roads lead to resistance","volume":"19","author":"Breidenstein","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jbiotec.2014.09.003","article-title":"Antibiotic resistance in Pseudomonas aeruginosa biofilms: Towards the development of novel anti-biofilm therapies","volume":"191","author":"Taylor","year":"2014","journal-title":"J. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1167\/iovs.06-0848","article-title":"Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of cornealepithelial wound healing","volume":"48","author":"Garrett","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38749","DOI":"10.1074\/jbc.M406044200","article-title":"Helix induction in antimicrobial peptides by alginate in biofilms","volume":"279","author":"Chan","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mulcahy, H., Charron-Mazenod, L., and Lewenza, S. (2008). Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000213"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2012.04.063","article-title":"Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen\u2019s egg chorioallantoic membrane and excised bovine cornea models","volume":"432","author":"Abdelkader","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.addr.2007.04.019","article-title":"The chick embryo and its chorioallantoic membrane (CAM) for the in vivo evaluation of drug delivery systems","volume":"59","author":"Vargas","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","first-page":"385","article-title":"Acute inflammation of the eyelid and cornea in Staphylococcus keratitis in the rabbit","volume":"40","author":"Sloop","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","first-page":"2904","article-title":"Staphylococcus corneal virulence in a new topical model of infection","volume":"42","author":"Hume","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0009-2797(00)00201-5","article-title":"Peroxidases","volume":"129","year":"2000","journal-title":"Chemico-Biol. Interact."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/gerona\/glp183","article-title":"Myeloperoxidase levels and mortality in frail community-living elderly individuals","volume":"65A","author":"Giovannini","year":"2010","journal-title":"J. Gerontol. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.1167\/iovs.16-19702","article-title":"Naringenin Eye Drops Inhibit Corneal Neovascularization by Anti-Inflammatory and Antioxidant Mechanisms","volume":"58","author":"Oguido","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1128\/AEM.02095-09","article-title":"Inhibitory Effect of Biocides on the Viable Masses and Matrices of Staphylococcus aureus and Pseudomonas aeruginosa Biofilms","volume":"76","author":"Horemans","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ymeth.2007.01.006","article-title":"Microtitre plate based antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals","volume":"42","author":"Sarker","year":"2007","journal-title":"Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0887-2333(96)00021-5","article-title":"Evaluation of a modified HET-CAM assay as a screening test for eye irritancy","volume":"10","author":"Gilleron","year":"1996","journal-title":"Toxicol. In Vitro"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2016.02.039","article-title":"Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles(EGCG-LNs): In vivo, in vitro and ex vivo studies","volume":"502","author":"Fangueiro","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jfo.2016.10.010","article-title":"Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models","volume":"40","author":"Ferreira","year":"2017","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_38","first-page":"377","article-title":"Methods for the study of irritation and toxicity of articles applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1944","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1442-9071.2004.00914.x","article-title":"New vehicle based on a microemulsion for topical ocular administration of dexamethasone","volume":"32","author":"Fialho","year":"2004","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_40","first-page":"1978","article-title":"Evidence for N-acetylmannosamine as an ocular receptor for, P. aeruginosa adherence to scarified cornea","volume":"28","author":"Hazlett","year":"1987","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:42:55Z","timestamp":1760186575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,4]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["toxins11040203"],"URL":"https:\/\/doi.org\/10.3390\/toxins11040203","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,4]]}}}