{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:48:43Z","timestamp":1787921323864,"version":"build-2784847793"},"reference-count":103,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","award":["88887.318820\/2019-00"],"award-info":[{"award-number":["88887.318820\/2019-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Multidrug-resistant Cryptococcus neoformans is an encapsulated yeast causing a high mortality rate in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells, in addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of ascorbic acid (AsA), no reactive oxygen species (ROS) were detected, and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. However, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH) ergosterol biosynthesis and induced the decoupling of cytochrome c (Cyt c) from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.<\/jats:p>","DOI":"10.3390\/antibiotics12020378","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["No Chance to Survive: Mo-CBP3-PepII Synthetic Peptide Acts on Cryptococcus neoformans by Multiple Mechanisms of Action"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7100-0927","authenticated-orcid":false,"given":"Tawanny K. B.","family":"Aguiar","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe P.","family":"Mesquita","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-275, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilton A. S.","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco \u00cd. R.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-1575","authenticated-orcid":false,"given":"Cleverson D. T.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f4mulo F.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Department of Fisheries Engineering, Federal University of Cear\u00e1 (UFC), Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso S.","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Fisheries Engineering, Federal University of Cear\u00e1 (UFC), Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8210-2016","authenticated-orcid":false,"given":"Luciana M. R.","family":"Alencar","sequence":"additional","affiliation":[{"name":"Laboratory of Biophysics and Nanosystems, Physics Department, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-481X","authenticated-orcid":false,"given":"Ralph","family":"Santos-Oliveira","sequence":"additional","affiliation":[{"name":"Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941-906, RJ, Brazil"},{"name":"Laboratory of Nanoradiopharmacy, Rio de Janeiro State University, Rio de Janeiro 23070-200, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1207-1140","authenticated-orcid":false,"given":"Jose T. A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-4434","authenticated-orcid":false,"given":"Pedro F. N.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Federal University of Cear\u00e1, Fortaleza 60451-970, CE, Brazil"},{"name":"Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-275, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s12281-021-00419-5","article-title":"Investigational Agents for the Treatment of Resistant Yeasts and Molds","volume":"15","author":"Seiler","year":"2021","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1080\/14656566.2021.1935868","article-title":"How Urgent Is the Need for New Antifungals?","volume":"22","author":"Stewart","year":"2021","journal-title":"Expert Opin. 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