Hostname: page-component-76fb5796d-qxdb6 Total loading time: 0 Render date: 2024-04-25T08:49:27.063Z Has data issue: false hasContentIssue false

Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in Crotalus durissus terrificus rattlesnake's venom gland

Published online by Cambridge University Press:  06 December 2017

Izabel Cristina Justino Bandeira
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Danya Bandeira-Lima
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Clarissa Perdigão Mello
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ticiana Praciano Pereira
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Ramon Róseo Paula Pessoa Bezerra De Menezes
Affiliation:
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Tiago Lima Sampaio
Affiliation:
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Cláudio Borges Falcão
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
Gandhi Rádis-Baptista*
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil Instituto de Ciências do Mar, Universidade Federal do Ceara, Fortaleza, CE, Brasil
Alice Maria Costa Martins*
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Ceará, Fortaleza, CE, Brasil
*
Authors for correspondence: Alice Maria Costa Martins, E-mail: martinsalice@gmail.com; Gandhi Rádis-Baptista, E-mail: radisbra@yahoo.com
Authors for correspondence: Alice Maria Costa Martins, E-mail: martinsalice@gmail.com; Gandhi Rádis-Baptista, E-mail: radisbra@yahoo.com

Abstract

Cathelicidins are antimicrobial peptides produced by humans and animals in response to various pathogenic microbes. Crotalicidin (Ctn), a cathelicidin-related vipericidin from the South American Crotalus durissus terrificus rattlesnake's venom gland, and its fragments have demonstrated antimicrobial and antifungal activity, similarly to human cathelicidin LL-37. In order to provide templates for the development of modern trypanocidal agents, the present study evaluated the antichagasic effect of these four peptides (Ctn, Ctn[1-14], Ctn[15-34] and LL-37). Herein, Ctn and short derived peptides were tested against the epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi Y strain (benznidazole-resistant strain) and cytotoxicity in mammalian cells was evaluated against LLC-MK2 lineage cells. Ctn inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease. Moreover, Ctn showed a high selective index against trypomastigote forms (>200). Ctn induced cell death in T. cruzi through necrosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as loss of membrane integrity and cell shrinkage, as observed through scanning electron microscopy. Overall, Ctn seems to be a promising template for the development of antichagasic agents.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adade, CM, Oliveira, IR, Pais, JA and Souto-Padrón, T (2013) Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways. Toxicon 69, 227239.Google Scholar
Adade, CM, Carvalho, AL, Tomaz, MA, Costa, TF, Godinho, JL, Melo, PA, Lima, AP, Rodrigues, JC, Zingali, RB and Souto-Padrón, T (2014) Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania. PLoS Neglected Tropical Diseases 8, e3252.CrossRefGoogle ScholarPubMed
Andrews, NW and Colli, W (1982) Adhesion and interiorization of Trypanosoma cruzi in mammalian cells. Journal of Protozoology 29, 264269.Google Scholar
Cavalcante, CS, Falcão, CB, Fontenelle, RO, Andreu, D and Rádis-Baptista, G (2016) Anti-fungal activity of Ctn[15-34], the C-terminal peptide fragment of crotalicidin, a rattlesnake venom gland cathelicidin. Journal of Antibiotics (Tokyo) 70, 231237.Google Scholar
Chatelain, E (2017) Chagas disease research and development: Is there light at the end of the tunnel? Computational and Structural Biotechnology Journal 15, 98103.Google Scholar
De Souza, W, De Carvalho, TMU and Barrias, ES (2010) Review on Trypanosoma cruzi: host cell interaction. International Journal of Cell Biology 2010, 295394. doi: 10.1155/2010/295394.Google Scholar
Falcao, CB, de La Torre, BG, Pérez-Peinado, C, Barron, AE, Andreu, D and Rádis-Baptista, G (2014) Vipericidins: a novel family of cathelicidin-related peptides from the venom gland of South American pit vipers. Amino Acids 46, 25612571.Google Scholar
Falcao, CB, Pérez-Peinado, C, de la Torre, BG, Mayol, X, Zamora-Carreras, H, Jiménez, , Rádis-Baptista, G and Andreu, D (2015) Structural dissection of crotalicidin, a rattlesnake venom cathelicidin, retrieves a fragment with antimicrobial and antitumor activity. Journal of Medicinal Chemistry 58, 85538563.Google Scholar
Lima, DB, Sousa, PL, Torres, AF, Rodrigues, KA, Mello, CP, Menezes, RR, Tessarolo, LD, Quinet, YP, de Oliveira, MR and Martins, AM (2016) Antiparasitic effect of Dinoponera quadriceps giant ant venom. Toxicon 120, 128132.Google Scholar
Mcgwire, BS and Kulkarni, MM (2010) Interactions of antimicrobial peptides with Leishmania and trypanosomes and their functional role in host parasitism. Experimental Parasitology 126, 397405.Google Scholar
McGwire, BS, Olson, CL, Tack, BF and Engman, DM (2003) Killing of African trypanosomes by antimicrobial peptides. Journal of Infectious Diseases 188, 146152.CrossRefGoogle ScholarPubMed
Mello, CP, Lima, DB, Menezes, RR, Bandeira, IC, Tessarolo, LD, Sampaio, TL, Falcão, CB, Rádis-Baptista, G and Martins, AM (2017) Evaluation of the antichagasic activity of batroxicidin, a cathelicidin-related antimicrobial peptide found in Bothrops atrox venom gland. Toxicon 130, 5662.Google Scholar
Nwaka, S and Hudson, A (2006) Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery 5, 941955.Google Scholar
Rádis-Baptista, G (2015) Vipericidins, snake venom cathelicidin-related peptides, in the milieu of reptilian antimicrobial polypeptides. In Snake Venoms. Gopalakrishnakoneal, P, Inagaki, H, Mukherjee, AK, Rahmy Carl-Wilhelm Vogel, TR (eds). The Netherlands: Springer, pp. 125.Google Scholar
Rodrigues, JH, Ueda-Nakamura, T, Corrêa, AG, Sangi, DP and Nakamura, CV (2014) A quinoxaline derivative as a potent chemotherapeutic agent, alone or in combination with benznidazole, against Trypanosoma cruzi. PLoS ONE 9, e85706.Google Scholar
Sani, MA and Separovic, F (2016) How membrane-active peptides get into lipid membranes. Accounts of Chemical Research 49, 11301138.Google Scholar
Souza, AL, Faria, RX, Calabrese, KS, Hardoim, DJ, Taniwaki, N, Alves, LA and De Simone, SG (2016) Temporizin and temporizin-1 peptides as novel candidates for eliminating Trypanosoma cruzi. PLoS ONE 11, e0157673.Google Scholar
Teixeira, V, Feio, MJ and Bastos, M (2012) Role of lipids in the interaction of antimicrobial peptides with membranes. Progress in Lipid Research 51, 149177.Google Scholar
Vanden Berghe, T, Grootjans, S, Goossens, V, Dondelinger, Y, Krysko, DV, Takahashi, N and Vandenabeele, P (2013) Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods 61, 117129.CrossRefGoogle ScholarPubMed
Vieira-Girão, PR, Falcão, CB, Rocha, IR, Lucena, HM, Costa, FH and Rádis-Baptista, G (2017) Antiviral activity of Ctn[15-34], A cathelicidin-derived eicosapeptide, against infectious myonecrosis virus in Litopenaeus vannamei primary hemocyte cultures. Food and Environmental Virology. doi: 10.1007/s12560-017-9285-5. [Epub ahead of print].Google Scholar
Wódz, K and Brzezińiska-Błaszczyk, E (2015) Cathelicidins – endogenous antimicrobial peptides. Postepy Biochemii 61, 93101.Google Scholar
World Health Organization (WHO) (2016) ‘Chagas disease (American trypanosomiasis)’. Fact sheet N° 340 Updated March 2016. World Health Organization, Geneva, Switzerland, Available at: http://www.who.int/mediacentre/factsheets/fs340/en/.Google Scholar
Zingales, B, Andrews, NW, Kuwajima, VY and Colli, W (1982) Cell surface antigens of Trypanosoma cruzi: possible correlation with the interiorization process in mammalian cells. Molecular & Biochemical Parasitology 6, 111124.Google Scholar
Zingales, B, Pereira, ME, Almeida, KA, Umezawa, ES, Nehme, NS, Oliveira, RP, Macedo, A and Souto, RP (1997) Biological parameters and molecular markers of clone CL Brener – the reference organism of the Trypanosoma cruzi genome project. Memorias do Instituto Oswaldo Cruz 92, 811814.CrossRefGoogle ScholarPubMed
Supplementary material: File

Bandeira et al supplementary material 1

Supplementary Figure

Download Bandeira et al supplementary material 1(File)
File 586.1 KB