Spider Venoms pp 333-344 | Cite as

Recent Insights in Latrodectus (“Black Widow” Spider) Envenomation: Toxins and Their Mechanisms of Action

  • Osmindo Rodrigues PiresJrEmail author
  • Wagner Fontes
  • Mariana S. CastroEmail author
Reference work entry
Part of the Toxinology book series (TOXI)


The Latrodectus genus (Araneae: Theridiidae) includes species commonly named black widow spiders. Due to highly potent neurotoxins present in Latrodectus venom, these spiders have medical interest. Envenomation is called Latrodectism and the symptoms include diaphoresis, hypertension, muscle cramping, weakness, and severe abdominal and/or back pain; however, cases of death are rare. The Latrodectus venom contains a cocktail of neurotoxic proteins collectively named latrotoxins (LTX). α-LTX strongly binds to a specific presynaptic receptor creating ionic pores, thus provoking a massive release of neurotransmitters. It displays no selectivity for specific synapse types and has no effect on non-neuronal cell types. Studies of Latrodectus venom, concerning toxin isolation, are mainly restricted to few species, although some molecular biology approaches reveal new putative latrotoxins in other Theridiidae species. This chapter offers a brief historical review and the current knowledge on Latrodectus venom and toxins.


Latrodectus Latrodectism Latrotoxins Neurotransmitter release 


  1. Akhunov AA, Makevnina LG, Golubenko Z, Paskhina TS. Kininase of the Latrodectus tredecimguttatus venom: a study of its enzyme substrate specificity. Immunopharmacology. 1996;32:160–2.CrossRefPubMedGoogle Scholar
  2. Bettini S, Maroli M. Venoms of theridiidae, genus Latrodectus. In: Bettini S, editor. Handbook of experimental pharmacology. Arthropod venoms. Berlin: Springer; 1978.CrossRefGoogle Scholar
  3. Bhere KV, Haney RA, Ayoub NA, Garb JE. Gene structure, regulatory control, and evolution of black widow venom latrotoxins. FEBS Lett. 2014;588:3891–7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bittner MA. Alpha-latrotoxin and its receptors CIRL (latrophilin) and neurexin 1 alpha mediate effects on secretion through multiple mechanisms. Biochimie. 2000;82(5):447–52.CrossRefPubMedGoogle Scholar
  5. Cavalieri M, Corvaja N, Grasso A. Immunocytological localization by monoclonal antibodies of α-latrotoxin in the venom gland of the spider Latrodectus tredecimguttatus. Toxicon. 1990;28:341–6.CrossRefPubMedGoogle Scholar
  6. Clark RF, Wethern-Kestner S, Vance MV, Gerkin R. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med. 1992;21:782–7.CrossRefPubMedGoogle Scholar
  7. Cunha SR, Mohler PJ. Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med. 2009;13(11–12):4364–76.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Danilevich VN, Grishin EV. The chromosomal genes for black widow spider neurotoxins do not contain introns. Bioorg Khim. 2000;26:933–9.PubMedGoogle Scholar
  9. Davletov BA, Shamotienko OG, Lelianova VG, Grishin EV, Ushkaryov YA. Isolation and biochemical characterization of a Ca2+-independent α-latrotoxin-binding protein. J Biol Chem. 1996;271:23239–45.CrossRefPubMedGoogle Scholar
  10. Duan ZG, Yan XJ, He XZ, Zhou H, Chen P, Cao R, Xiong JX, Hu WJ, Wang XC, Liang SP. Extraction and protein component analysis of venom from the dissected venom glands of Latrodectus tredecimguttatus. Comp Biochem Physiol B Biochem Mol Biol. 2006;145:350–7.CrossRefPubMedGoogle Scholar
  11. Duan Z, Yan X, Cao R, Liu Z, Wang X, Liang S. Proteomic analysis of Latrodectus tredecimguttatus venom for uncovering potential Latrodectism-related proteins. J Biochem Mol Toxicol. 2008;22:328–36.CrossRefPubMedGoogle Scholar
  12. Dulubova IE, Krasnoperov VG, Khvotchev MV, Pluzhnikov KA, Volkova TM, Grishin EV, Vais H, Bell DR, Usherwood PN. Cloning and structure of δ-latroinsectotoxin, a novel insect-specific member of the latrotoxin family: functional expression requires C-terminal truncation. J Biol Chem. 1996;271:7535–43.CrossRefPubMedGoogle Scholar
  13. Food and Drug Administration. U.S. Food and drug administration; 2015. Online at, Accessed 31 Aug 2015.
  14. Garb JE, Hayashi CY. Molecular evolution of α-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom. Mol Biol Evol. 2013;30:999–1014.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Garb JE, Gonzalez A, Gillespie RG. The black widow spider genus Latrodectus: phylogeny, biogeography and invasion history. Mol Phylogenet Evol. 2004;31:1127–42.CrossRefPubMedGoogle Scholar
  16. Gasparini S, Kiyatkin N, Drevet P, Boulain JC, Tacnet F, Ripoche P, Forest E, Grishin E, Ménez A. The low molecular weight protein which co-purifies with α-latrotoxin is structurally related to crustacean hyperglycemic hormones. J Biol Chem. 1994;269:19803–9.PubMedGoogle Scholar
  17. Grasso A. Preparation and properties of a neurotoxin purified fromthe venom of black widow spider (Latrodectus mactans tredecimguttatus). Biochim Biophys Acta. 1976;439:400–12.Google Scholar
  18. Grishin EV. Black widow spider toxins: the present and the future. Toxicon. 1998;36:1693–701.CrossRefPubMedGoogle Scholar
  19. Grishin EV, Himmelreich NH, Pluzhnikov KA, Pozdnyakova NG, Storchak LG, Volkova TM, Woll PG. Modulation of functional activities of the neurotoxin from black widow spider venom. FEBS Lett. 1993;336:205–7.CrossRefPubMedGoogle Scholar
  20. Hahn IH, Lewin NA. Arthropods. In: Flomenbaum NE, Goldfrank L, Hoffman R, Howland MA, Lewin N, Nelson L, editors. Goldfrank’s toxicologic emergencies. 8th ed. New York: McGraw-Hill; 2006. p. 1603–22.Google Scholar
  21. Haney RA, Ayoub NA, Clarke TH, et al. Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics. BMC Genomics. 2014;15:366.CrossRefPubMedPubMedCentralGoogle Scholar
  22. He Q, Duan Z, Yu Y, Liu Z, Liu Z, Liang S. The venom gland transcriptome of Latrodectus tredecimguttatus revealed by deep sequencing and cDNA library analysis. PLoS ONE. 2013;8(11):e81357.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Henkel AW, Sankaranarayanan S. Mechanisms of alpha-latrotoxin action. Cell Tissue Res. 1999;296(2):229–33.CrossRefPubMedGoogle Scholar
  24. Horni A, Weickmann D, Hesse M. The main products of the low molecular mass fraction in the venom of the spider Latrodectus menavodi. Toxicon. 2001;39(2–3):425–8.CrossRefPubMedGoogle Scholar
  25. Ichtchenko K, Khvotchev M, Kiyatkin N, Simpson L, Sugita S, Südhof TC. α-Latrotoxin action probed with recombinant toxin: receptors recruit α-latrotoxin but do not transduce an exocytotic signal. EMBO J. 1998;17:6188–99.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Isbister GK, Gray MR. Latrodectism: a prospective cohort study of bites by formally identified redback spiders. Med J Aust. 2003;179:88–91.PubMedGoogle Scholar
  27. Kiyatkin NI, Dulubova IE, Chekhovskaya IA, et al. Cloning and structure of cDNA encoding α-latrotoxin from black widow spider venom. FEBS Lett. 1990;270:127–31.CrossRefPubMedGoogle Scholar
  28. Kiyatkin N, Dulubova I, Chekhovskaya I, Lipkin A, Grishin E. Structure of the low molecular weight protein copurified with alpha-latrotoxin. Toxicon. 1992;30(7):771–4.CrossRefPubMedGoogle Scholar
  29. Kiyatkin NI, Kulikovskaya IM, Grishin EV, et al. Functional characterization of black widow spider neurotoxins synthesised in insect cells. Eur J Biochem. 1995;230:854–9.CrossRefPubMedGoogle Scholar
  30. Krasnoperov V, Bittner MA, Mo W, Buryanovsky L, Neubert TA, Holz RW, Ichtchenko K, Petrenko AG. Protein tyrosine phosphatase-σ is a novel member of the functional family of α-latrotoxin receptors. J Biol Chem. 2002;277:35887–95.CrossRefPubMedGoogle Scholar
  31. Kuhn-Nentwig L, Stöcklin R, Nentwig W. Venom composition and strategies in spiders: is everything possible? In: Casas J, editor. Advances in insect physiology, vol. 60. Burlington: Academic; 2011. p. 1–86.Google Scholar
  32. Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF, Ushkaryov YA. α-Latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem. 1997;272:21504–8.CrossRefPubMedGoogle Scholar
  33. Magazanik LG, Fedorova IM, Kovalevskaya GI, Pashkov VN, Bulgakov OV, Grishin EV. Selective presynaptic insectotoxin (α-latroinsectotoxin) isolated from black widow spider venom. Neuroscience. 1992;46:181–8.CrossRefPubMedGoogle Scholar
  34. Maretic Z. Latrodectism: variations in clinical manifestations provoked by Latrodectus species of spiders. Toxicon. 1983;21:457–66.CrossRefPubMedGoogle Scholar
  35. McCrone JD. Comparative lethality of several Latrodectus venoms. Toxicon. 1964;2:201–3.CrossRefPubMedGoogle Scholar
  36. Moss HS, Binder LS. A retrospective review of black widow spider envenomation. Ann Emerg Med. 1987;16(2):188–92.CrossRefPubMedGoogle Scholar
  37. Offerman SR, Daubert GP, Clark RF. The treatment of black widow spider envenomation with antivenin Latrodectus mactans: a case series. Perm J. 2011;15(3):76–81.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Orlova EV, Rahman MA, Gowen B, Volynski KE, Ashton AC, Manser C, van Heel M, Ushkaryov YA. Structure of α-latrotoxin oligomers reveals that divalent cation-dependent tetramers form membrane pores. Nat Struct Biol. 2000;7:48–53.CrossRefPubMedGoogle Scholar
  39. Pansa MC, Natalizi GM, Bettini S. 5-hydroxytryptamine content of Latrodectus mactans tredecimguttatus venom from gland extracts. Toxicon. 1972;10:85–6.CrossRefPubMedGoogle Scholar
  40. Petrenko AG, Ullrich B, Missler M, Krasnoperov V, Rosahl TW, Südhof TC. Structure and evolution of neurexophilin. J Neurosci. 1996;16:4360–9.PubMedGoogle Scholar
  41. Pneumatikos IA, Galiatsou E, Goe D, Kitsakos A, Nakos G, Vougiouklakis TG. Acute fatal toxic myocarditis after black widow spider envenomation. Ann Emerg Med. 2003;41(1):158.CrossRefPubMedGoogle Scholar
  42. Ramialiharisoa A, de Haro L, Jouglard J, Goyffon M. Latrodectism in Madagascar. Med Trop (Mars). 1994;54(2):127–30.Google Scholar
  43. Rohou A, Nield J, Ushkaryov YA. Insecticidal toxins from black widow spider venom. Toxicon. 2007;15:531–49.CrossRefGoogle Scholar
  44. Russell FE. Phosphodiesterase of some snake and arthropod venoms. Toxicon. 1966;4:153–4.CrossRefPubMedGoogle Scholar
  45. Shatursky OY, Pashkov VN, Bulgacov OV, Grishin EV. Interaction of α-latroinsectotoxin from Latrodectus mactans venom with bilayer lipid membranes. Biochim Biophys Acta. 1995;1233:14–20.CrossRefPubMedGoogle Scholar
  46. Smith DS, Russell FE. Structure of the venom gland of the black widow spider Latrodectus mactans. A preliminary light and electron microscopic study. In: Russell FE, Saunders PR, editors. Animal toxins. Oxford: Pergamon; 1966. p. 1–15.Google Scholar
  47. Tzeng MC, Cohen RS, Siekevitz P. Release of neurotransmitters and depletion of synaptic vesicles in cerebral cortex slices by alpha-latrotoxin from black widow spider venom. Proc Natl Acad Sci. 1978;75:4016–20.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Ushkaryov YA, Petrenko AG, Geppert M. Neurexins: synaptic cell surface proteins related to the α-latrotoxin receptor and laminin. Science. 1992;257:50–6.CrossRefPubMedGoogle Scholar
  49. Ushkaryov YA, Rohou A, Sugita S. α-Latrotoxin and its receptors. Handb Exp Pharmacol. 2008;184:171–206.CrossRefPubMedGoogle Scholar
  50. Volkova TM, Pluzhnikov KA, Woll PG, Grishin EV. Low-molecular-weight components from black-widow spider venom. Toxicon. 1995;33:483–9.CrossRefPubMedGoogle Scholar
  51. Volynski KE, Nosyreva ED, Ushkaryov YA, Grishin EV. Functional expression of α-latrotoxin in baculovirus system. FEBS Lett. 1999;442:25–8.CrossRefPubMedGoogle Scholar
  52. World Spider Catalog. World Spider Catalog. Natural History Museum Bern; 2015. Online at, version 16.5, Accessed 26 July 2015.

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© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Laboratory of Toxinology, Department of Physiological Sciences/IBUniversity of BrasiliaBrasilia-DFBrazil
  2. 2.Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology/IBUniversity of BrasiliaBrasilia-DFBrazil

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