Repurposing a peptide toxin from wasp venom intoantiinfectives with dual antimicrobial andimmunomodulatory properties

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dc.creatorSilva, Osmar Nascimento
dc.creatorTorres, Marcelo Der Torossian
dc.creatorCao, Jicong
dc.creatorAlves, Eliane Santana Fernandes
dc.creatorRodrigues, Leticia Valvassori
dc.creatorResende, Jarbas Magalhães
dc.creatorLiao, Luciano Morais
dc.creatorPorto, William Farias
dc.creatorFensterseifer, Isabel Cristina Marques
dc.creatorLu, Timothy K. T.
dc.creatorFranco, Octavio Luiz
dc.creatorFuente Nunez, Cesar de la
dc.date.accessioned2024-02-28T10:10:20Z
dc.date.available2024-02-28T10:10:20Z
dc.date.issued2020-10-27
dc.description.abstractNovel antibiotics are urgently needed to combat multidrug-resistant pathogens. Venoms represent previously untapped sources of novel drugs. Here we repurposed mastoparan-L, the toxic active principle derived from the venom of the wasp Vespula lewisii, into synthetic antimicrobials. We engineered within its N terminus a motif conserved among natural peptides with potent immunomodulatory and antimicrobial activities. The resulting peptide, mast-MO, adopted an α-helical structure as determined by NMR, exhibited increased antibacterial properties comparable to standard-of-care antibiotics both in vitro and in vivo, and potentiated the activity of different classes of antibiotics. Mechanism-of-action studies revealed that mast-MO targets bacteria by rapidly permeabilizing their outer membrane. In animal models, the peptide displayed direct antimicrobial activity, led to enhanced ability to attract leukocytes to the infection site, and was able to control inflammation. Permutation studies depleted the remaining toxicity of mast-MO toward human cells, yielding derivatives with antiinfective activity in animals. We demonstrate a rational design strategy for repurposing venoms into promising antimicrobials.
dc.identifier.citationSILVA, Osmar N. et al. Repurposing a peptide toxin from wasp venom into antiinfectives with dual antimicrobial and immunomodulatory properties. Proceedings of the National Academy of Sciences, Washington, v. 117, n. 43, p. 26936-26945, 2020. DOI: 10.1073/pnas.2012379117. Disponível em: https://www.pnas.org/doi/full/10.1073/pnas.2012379117. Acesso em: 16 fev. 2024.
dc.identifier.doi10.1073/pnas.2012379117
dc.identifier.issn0027-8424
dc.identifier.issne-1091-6490
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/24437
dc.language.isoeng
dc.publisher.countryEstados unidos
dc.publisher.departmentInstituto de Química - IQ (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectVenoms
dc.subjectAntimicrobial peptides
dc.subjectImmunomodulatory peptides
dc.subjectAntiinfectives
dc.subjectStructure-activity relationship
dc.titleRepurposing a peptide toxin from wasp venom intoantiinfectives with dual antimicrobial andimmunomodulatory properties
dc.typeArtigo

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