Isolation and partial characterization of an anti-bothropic complex from the serum of South American Didelphidae

Perales, Jonás; Moussatché, H.; Marangoni, Sérgio; Oliveira, Benedito; Domont, Gilberto B.

doi:10.1016/0041-0101(94)90353-0

Cited by 40 publications

(23 citation statements)

References 28 publications

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“…In fact, resistance to snake venom has been reported from a few prey species, mostly rodents [26], [52], [60], [61], but also from a wide array of animals that eat snakes [29], [62]–[65]. However, rapid adaptive evolution of genes conferring venom resistance has not previously been demonstrated, nor have the molecular substitutions responsible for venom resistance been examined in any substantive detail (except at the AChR locus described above).…”

Section: Resultsmentioning

confidence: 99%

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Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

Jansa

Voss

2011

PLoS ONE

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The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role.

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Section: Resultsmentioning

confidence: 99%

“…1). It is also known that the brown four-eyed opossum ( Metachirus ), the sister taxon to Didelphini, is not venom resistant [29].…”

Section: Introductionmentioning

confidence: 99%

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

Jansa

Voss

2011

PLoS ONE

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“…Opossum serum was obtained from blood collected by cardiac puncture as described previously [25]. Serum was dialyzed for 24 h at 4 °C against the column equilibration buffer.…”

Section: Purification Of Dm64mentioning

confidence: 99%

Functional analysis of DM64, an antimyotoxic protein with immunoglobulin‐like structure from Didelphis marsupialis serum

Rocha

Lomonte

Neves-Ferreira

et al. 2002

European Journal of Biochemistry

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Bothrops snake venoms are known to induce local tissue damage such as hemorrhage and myonecrosis. The opossum Didelphis marsupialis is resistant to these snake venoms and has natural venom inhibitors in its plasma. The aim of this work was to clone and study the chemical, physicochemical and biological properties of DM64, an antimyotoxic protein from opossum serum. DM64 is an acidic protein showing 15% glycosylation and with a molecular mass of 63 659 Da when analysed by MALDI-TOF MS. It was cloned and the amino acid sequence was found to be homologous to DM43, a metalloproteinase inhibitor from D. marsupialis serum, and to human a 1 B-glycoprotein, indicating the presence of five immunoglobulin-like domains. DM64 neutralized both the in vivo myotoxicity and the in vitro cytotoxicity of myotoxins I (mt-I/Asp49) and II (mt-II/Lys49) from Bothrops asper venom. The inhibitor formed noncovalent complexes with both toxins, but did not inhibit the PLA 2 activity of mt-I. Accordingly, DM64 did not neutralize the anticoagulant effect of mt-I nor its intracerebroventricular lethality, effects that depend on its enzymatic activity, and which demonstrate the dissociation between the catalytic and toxic activities of this Asp49 myotoxic PLA 2 . Furthermore, despite its similarity with metalloproteinase inhibitors, DM64 presented no antihemorrhagic activity against Bothrops jararaca or Bothrops asper crude venoms, and did not inhibit the fibrinogenolytic activity of jararhagin or bothrolysin. This is the first report of a myotoxin inhibitor with an immunoglobulin-like structure isolated and characterized from animal blood.

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“…They concluded that the presence of oprin in opossum serum may partially account for the resistance of this marsupial to the localized effects of rattlesnake envenomation. Perales et al (1994) isolated an anti-bothropic fraction (ABF) from the sera of several South American Didelphidae (D. marsupialis, P. opossum, and L. crassicaudata). They found that ABF has anti-B.…”

Section: Animals Having Anti-hemorrhagic Factorsmentioning

confidence: 99%

Part 1: Lethal Toxin Neutralizing Factor From Opossum Serum

Lipps¹

2008

Toxin Reviews

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Currently, the use of anti-venoms is the only available treatment for envenomations caused by poisonous animals, namely snake, scorpion, spider, tick, and jellyfish. Anti-venoms are generally produced in big animals, mostly in horses. A large percentage of the population in some regions is allergic to horse proteins. Several animals are known to be resistant to snakebites, and the anti-hemorrhagic and anti-lethal components have been isolated from sera of opossum, mongoose, meerkat, and hedgehog, as well as from poisonous and nonpoisonous snakes. Lethal toxin neutralizing factor (LTNF) was isolated in purity from opossum (D. virginiana) serum by high-pressure liquid chromatography. (Crotalidae, Elapidae, Viperidae, and Hydrophiidae) is prevented in mice by subsequent intraperitoneal inoculation of LTNF. Furthermore, LTNF neutralizes the lethality of scorpion and bee venoms and toxins from various animal, plant, and bacterial sources. Thus, natural LTNF from opossum serum has potential as a universal therapy for envenomations and other toxin exposure caused by animals, plants, and bacteria. The molecular weight of LTNF is 63 kDa, and it does not form precipitates with venoms or toxins by immune diffusion test. Death due to intraperitoneal injection of a predetermined lethal dose of venom from major families of snakes

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Isolation and partial characterization of an anti-bothropic complex from the serum of South American Didelphidae

Cited by 40 publications

References 28 publications

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

Functional analysis of DM64, an antimyotoxic protein with immunoglobulin‐like structure from Didelphis marsupialis serum

Part 1: Lethal Toxin Neutralizing Factor From Opossum Serum

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