Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon

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Sousa, Leijiane F. ; Portes-Junior, Jose A. ; Nicolau, Carolina A. ; Bernardoni, Juliana L. ; Nishiyama-, Jr., Milton Y. ; Amazonas, Diana R. ; Freitas-de-Sousa, Luciana A. ; Mourao, Rosa H. V. ; Chalkidis, Hipocrates M. ; Valente, Richard H. ; Moura-da-Silva, Ana M.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOMICS; v. 159, p. 32-46, APR 21 2017.
• Citações Web of Science: 16

Resumo

Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-flrme upland forest and vcirzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA(2)s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from varzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA(2)s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silica prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. Biological significance: In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (varzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not efficiently neutralized by Bothrops antivenom. Thus, using a functional proteomic approach, we highlighted intraspecific differences in B. atrox venom that could impact both in the ecology of snakes but also in the treatment of snake bite patients in the region. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 14/13124-2 - Variabilidade em venenos de serpentes Bothrops atrox no oeste do Pará: implicações ecológicas e para a fisiopatologia dos envenenamentos
• Beneficiário: Leijiane Figueira de Sousa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/16277-9 - Variabilidade na composição dos venenos botrópicos e implicações funcionais da presença de diferentes metaloproteinases na composição dos mesmos
• Beneficiário: Ana Maria Moura da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/26058-8 - Inibição de metaloproteinases de mamíferos e de venenos de serpentes pelo pró-domínio recombinante da jararagina e seus fragmentos peptídicos
• Beneficiário: Ana Maria Moura da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/13592-6 - Diferenças estruturais entre duas SVMPs de classe P-I do veneno de Bothrops neuwiedi
• Beneficiário: Juliana Lech Bernardoni
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado