Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?

Luiza Helena Gremski,Pedro Henrique De Caires Schluga,Andrea Senff-Ribeiro,Zelinda Schemczssen-Graeff,Fernando Hitomi Matsubara,Marianna Boia-Ferreira,Hanna Câmara Da Justa,Silvio Sanches Veiga,Ana Carolina Martins Wille,Antonielle Beatriz Baldissera,Isabel De Oliveira Leite

doi:10.1590/1678-9199-jvatitd-2020-0188

Abstract

Accidents caused by the bites of brown spiders (Loxosceles) generate a clinical condition that often includes a threatening necrotic skin lesion near the bite site along with a remarkable inflammatory response. Systemic disorders such as hemolysis, thrombocytopenia, and acute renal failure may occur, but are much less frequent than the local damage. It is already known that phospholipases D, highly expressed toxins in Loxosceles venom, can induce most of these injuries. However, this spider venom has a great range of toxins that probably act synergistically to enhance toxicity. The other protein classes remain poorly explored due to the difficulty in obtaining sufficient amounts of them for a thorough investigation. They include astacins (metalloproteases), serine proteases, knottins, translationally controlled tumor proteins (TCTP), hyaluronidases, allergens and serpins. It has already been shown that some of them, according to their characteristics, may participate to some extent in the development of loxoscelism. In addition, all of these toxins present potential application in several areas. The present review article summarizes information regarding some functional aspects of the protein classes listed above, discusses the directions that could be taken to materialize a comprehensive investigation on each of these toxins as well as highlights the importance of exploring the full venom repertoire.

Highlights

Accidents involving brown spider bites are endemic in South and Southeast regions of Brazil, where they have caused more than 80,000 notifications over the past ten years [1]
Two families of toxins belonging to the group of highly expressed toxins will be addressed as well as the other families of toxins belonging to the group of low-expressed toxins (Figure 1)
The allergen from L. intermedia venom has a molecular mass of 42 kDa and presents epitopes that cross reacted with anti-venom sera developed using crude venoms from L. laeta and L. gaucho, suggesting that these molecules are conserved in different species of the Loxosceles genus

Summary

Background

Accidents involving brown spider bites are endemic in South and Southeast regions of Brazil, where they have caused more than 80,000 notifications over the past ten years [1]. Among the toxins with high expression, phospholipases D are undoubtedly the most studied and well characterized molecules from the biochemical and functional standpoints They are highly conserved toxins among the various species of Loxosceles spiders described in the literature, comprising a family of toxins with intra- and inter-species occurrence coverage. Two families of toxins belonging to the group of highly expressed toxins (knottins and astacins) will be addressed as well as the other families of toxins belonging to the group of low-expressed toxins (hyaluronidases, allergens, TCTP, serine proteases, and serpins) (Figure 1) These toxins are not individually involved in all venom deleterious activities like phospholipases D, recent studies point out that some of these molecules have a relevant participation in the framework of loxoscelism pathophysiology, in addition to being a potential target for the development of biotechnological resources or for the understanding of molecular and cellular processes

Methodology

Findings

Conclusion