Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

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Dematei, Anderson ^{[1, 2]} ; Nunes, Joao B. ^{[3, 4]} ; Moreira, Daniel C. ^[2] ; Jesus, Jessica A. ^[5] ; Laurenti, Marcia D. ^[6] ; Mengarda, Ana C. A. ^[7] ; Vieira, Maria Silva ^{[8, 9]} ; do Amaral, Constanca Pais ^[10] ; Domingues, Marco M. ^[10] ; de Moraes, Josue ^[7] ; Passero, Luiz F. D. ^{[5, 6]} ; Brand, Guilherme ^[4] ; Bessa, Lucinda J. ^[11] ; Wimmer, Reinhard ^[12] ; Kuckelhaus, Selma A. S. ^[2] ; Tomas, Ana M. ^{[13, 14]} ; Santos, Nuno C. ^[10] ; Placido, Alexandra ^[11] ; Eaton, Peter ^{[11, 15]} ; Leite, Jose Roberto S. A. ^{[1, 2]}

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^[1] Univ Brasilia, Ctr Trop Med, NMT, Fac Med, NuPMIA, BR-70910900 Brasilia, DF - Brazil

^[2] Univ Brasilia, Fac Med, Res Ctr Morphol & Appl Immunol, NuPMIA, BR-70910900 Brasilia, DF - Brazil

^[3] Univ Brasilia, Res Ctr Morphol & Appl Immunol, NuPMIA, Fac Med, LSAB, Inst Chem, BR-70910900 Brasilia, DF - Brazil

^[4] Univ Brasilia, Inst Chem, Lab Synth & Anal Biomol, LSAB, BR-70910900 Brasilia, DF - Brazil

^[5] Sao Paulo State Univ, Inst Biosci, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Med, Dept Pathol, Lab Pathol Infect Dis, BR-05508060 Sao Paulo - Brazil

^[7] Univ Guarulhos, NPDN, Res Ctr Neglected Dis, BR-07023070 Guarulhos - Brazil

^[8] Univ Porto, I3S, Inst Res & Innovat Hlth, Inst Mol & Cellular Biol, P-4099002 Porto - Portugal

^[9] Univ Porto, IBMC, Inst Mol & Cellular Biol, P-4099002 Porto - Portugal

^[10] Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon - Portugal

^[11] Univ Porto, Fac Sci, LAQV REQUIMTE, Dept Chem & Biochem, P-4099002 Porto - Portugal

^[12] Aalborg Univ, Dept Chem & Biosci, DK-9220 Aalborg - Denmark

^[13] Univ Porto, Abel Salazar Inst Biomed Res, Inst Res & Innovat Hlth, IBMC, Inst Mol & Cellular Biol, I3S, P-4099002 Porto - Portugal

^[14] Univ Porto, Abel Salazar Inst Biomed Res, ICBAS, P-4099002 Porto - Portugal

^[15] Univ Lincoln, Sch Chem, Bridge, Joseph Banks Labs, Lincoln LN6 7TS - England

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 84, n. 6, p. 1787-1798, JUN 25 2021.
• Citações Web of Science: 0

Resumo

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, Bab(C(C-2.15Phe) and BabcC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections. (AU)

• Processo FAPESP: 19/25905-2 - Avaliação pré-clínica para administração oral de formulações nanoestruturadas contendo fármacos com atividade anti-helmíntica
• Beneficiário: Ana Carolina Araujo Mengarda
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/24077-6 - Estudos pré-clínicos de tratamentos não invasivos nas leishmanioses
• Beneficiário: Luiz Felipe Domingues Passero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular