Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis

Abstract

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. were identified in L. muta and L. stenophrys venoms. In addition, both venoms contained a large number of bradykinin-potentiating peptides (BPP) and a C-type natriuretic peptide (C-NP). BPPs and C-NP comprised around 15% of the total venom proteins. In both species, the most abundant proteins were Zn 2+ -metalloproteinases (32-38%) and serine proteinases (25-31%), followed by PLA 2 s (9-12%), galactose-specific C-type lectin (4-8%), L-amino acid oxidase (LAO, 3-5%), CRISP (1.8%; found in L. muta but not in L. stenophrys), and NGF (0.6%).On the other hand, only six L. muta venom-secreted proteins matched any of the previously reported 11 partial or full-length venom gland transcripts, and venom proteome and transcriptome depart in their relative abundances of different toxin families. As expected from their close phylogenetic relationship, the venoms of L. muta and L. stenophrys share (or contain highly similar) proteins, in particular BPPs, serine proteinases, a galactose-specific C-type lectin, and LAO. However, they dramatically depart in their respective PLA 2 complement. Intraspecific quantitative and qualitative differences in the expression of PLA 2 molecules were found when the venoms of five L. muta specimens (3 from Bolivia and 2 from Peru) and the venom of the same species purchased from Sigma were compared.These observations indicate that these class of toxins represents a rapidly-evolving Author's personal copy gene family, and suggests that functional differences due to structural changes in PLA 2 s molecules among these snakes may have been a hallmark during speciation and adaptation of diverging snake populations to new ecological niches, or competition for resources in existing ones. Our data may contribute to a deeper understanding of the biology and ecology of these snakes, and may also serve as a starting point for studying structure-function correlations of individual toxins.

Venoms, venomics, antivenomics

“…Firstly, these messengers may exhibit transient, individual or a temporal expression patterns over the life time of the snake. Alternatively, mRNAs whose predicted polypeptides were not found to be secreted in venom may represent very low abundance toxins that play a hitherto unrecognised physiological function in the venom gland, or may simply represent a hidden repertoire of non-translated orphan molecules which may eventually become functional for the adaptation of snakes to Table 1 Overview of the relative occurrence of proteins (in percentage of the total HPLC-separated proteins) of the toxin families in the venoms of Sistrurus catenatus catenatus (SCC), Sistrurus catenatus tergeminus (SCT), and Sistrurus catenatus edwardsii (SCE) from USA [34]; Sistrurus miliarius barbouri (SMB) from USA [52]; the Tunisian snakes Cerastes cerastes cerastes (CCC), Cerastes vipera (CV) and Macrovipera lebetina transmediterranea (MLT) [48]; African Bitis arietans (BA) [50]; Bitis gabonica gabonica (BGG) [49]; Bitis gabonica rhinoceros (BGR), Bitis nasicornis (BN), and Bitis caudalis (BC) [56]; Echis ocellatus (EO) [51]; Lachesis muta (LM) [53]; Crotalus atrox (CA), and Agkistrodon contortrix contortrix (ACC) from USA (Calvete et al, unpublished); Armenian vipers Macrovipera lebetina obtusa (Mlo), and Vipera raddei (Vr) [54]; Atropoides picadoi (Api), and Atropoides mexicanus (Amex) [57] from Costa Rica; Bothrops asper (Bas) from the Caribbean (C) and the Pacific versants of Costa Rica [60]; Lesser Antillean pitvipers Bothrops caribbaeus (Bcar) (Santa Lucía), and Bothrops lanceolatus (Blan) (Martinique) [58]; Brazilian Bothrops fonsecai (Bfon), and Bothrops cotiara (Bco) [59]; Bothriechis lateralis (Bolat), and Bothriechis schlegelii (Bosch) [55] from Costa Rica; and Lachesis stenophrys (Lste) [53] changing ecological niches and prey habits. These data suggest that the final composition of venom is influenced by transcriptional and post-translational mechanisms that may be more complex than previously appreciated.…”

Development of a sensitive enzyme immunoassay (ELISA) for specific identification of Lachesis acrochorda venom

“…And as previously mentioned, some differences among Lachesis species had been observed (23). Furthermore, geographical variations in the venom components demand the development of regional immunodiagnostic tests specific to snakes that inhabit a given region (25).…”

“…A recent study to develop a proteomic characterization of venoms of L. muta from Brazil and L. stenophrys from Costa Rica revealed that these venoms share (or contain highly similar) proteins, in particular bradykinin-potentiating/ C-natriuretic peptide (BPPs), serine proteinases, a galactose-specific C-type lectin, and L-amino acid oxidase (LAO). However, they dramatically differ in their respective PLA 2 complement (23).…”

Atividade tóxica da peçonha de <i>Lachesis muta rhombeata</i> e produção de fragmentos de anticorpos humanos (scFv) contra a peçonha bruta

“…Algumas atividades farmacológicas já foram descritas como formação de edemas, citotoxicidade, agregação plaquetária, ação hipotensiva, apoptose de células endoteliais, o que pode contribuir para o sangramento prolongado na parede dos vasos danificados pela mordida, entre outras (Ahn et al, 1997;Ali et al, 2000;Braga et al, 2008;Li et al, 1994;Suhr and Kim, 1996). Apesar de bem descritas nas peçonhas de diversas serpentes, ainda existem poucos estudos descrevendo as Laminoácido oxidases presentes em peçonhas laquéticas (Kuch et al, 1996;Sanz et al, 2008).…”

“…Entretanto, não é incomum encontrar serpentes com até 3,0 metros de comprimento (Sanz et al, 2008). Essa família ainda engloba dois outros gêneros de considerável importância, Crotalus e Bothrops (Damico et al, 2005a).…”