Highlights in the knowledge of brown spider toxins

Abstract

Brown spiders are venomous arthropods that use their venom for predation and defense. In humans, bites of these animals provoke injuries including dermonecrosis with gravitational spread of lesions, hematological abnormalities and impaired renal function. The signs and symptoms observed following a brown spider bite are called loxoscelism. Brown spider venom is a complex mixture of toxins enriched in low molecular mass proteins (4–40 kDa). Characterization of the venom confirmed the presence of three highly expressed protein classes: phospholipases D, metalloproteases (astacins) and insecticidal peptides (knottins). Recently, toxins with low levels of expression have also been found in Loxosceles venom, such as serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like toxins and histamine-releasing factors. The toxin belonging to the phospholipase-D family (also known as the dermonecrotic toxin) is the most studied class of brown spider toxins. This class of toxins single-handedly can induce inflammatory response, dermonecrosis, hemolysis, thrombocytopenia and renal failure. The functional role of the hyaluronidase toxin as a spreading factor in loxoscelism has also been demonstrated. However, the biological characterization of other toxins remains unclear and the mechanism by which Loxosceles toxins exert their noxious effects is yet to be fully elucidated. The aim of this review is to provide an insight into brown spider venom toxins and toxicology, including a description of historical data already available in the literature. In this review article, the identification processes of novel Loxosceles toxins by molecular biology and proteomic approaches, their biological characterization and structural description based on x-ray crystallography and putative biotechnological uses are described along with the future perspectives in this field.

Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential

“…Aiming to better understand this, we have focused on the SMaseD toxins, which play a key role in loxoscelism. These enzymes have been widely studied and characterized regarding their preferential substrates [48,49], structural basis [1,2,50,51], toxicity [5,52], immunogenicity [53,54] and representativeness in the whole venom [55]. SMases D are also designated dermonecrotic toxins as their recombinant forms have shown to reproduce most of the toxic effects observed in loxoscelism, including dermonecrotic lesions and antigenic properties of the venom [5].…”

“…To date the Loxosceles genus is comprised of 139 described spider species, differentially distributed and found in all five continents where different species have been reported [1]. In Brazil, L. intermedia, Toxins 2020, 12, 256; doi:10.3390/toxins12040256 www.mdpi.com/journal/toxins L. gaucho, and L. laeta are of particular medical concern, as in 2019 the number of reported envenomations was 8490, of which 11 were fatal for humans [2,3].…”

Forty Years of the Description of Brown Spider Venom Phospholipases-D

“…At the bite site, the cutaneous symptoms are edema, erythema and dermonecrosis with gravitational spreading of lesion (the characteristic hallmark of envenoming). The systemic condition, which is less common, may lead to death and includes hematological changes such as intravascular hemolysis, disseminated intravascular coagulation and thrombocytopenia, as well as acute renal failure [1][2][3][4][5][6]. The volume of venom injected at the time of the bite is low, normally just a few microliters and contains between 60 and micrograms of protein [7].…”

“…In addition, mutant versions of the enzyme supported the understanding of the binding to their lipid substrates, especially with choline-containing phospholipids, such as sphingomyelin and lysophosphatidylcholine. In this sense, the region containing three aromatic amino acid residues Y228, Y229, and W230, which are conserved in all the isoforms of Loxosceles venom PLDs with high catalytic and biological activities, has been postulated as playing an important role in the binding and orientation of the substrate relative to the catalytic site [6]. The explanation for such a change in these activities would be that, in the wild-type form, the region rich in aromatic residues (Y228, Y229, and W230) would interact with the hydrophilic head of the substrates by cation-π bonds, with emphasis on the choline, as previously shown for other PLDs [69,70].…”

Not so Dangerous After All? Venom Composition and Potency of the Pholcid (Daddy Long-Leg) Spider Physocyclus mexicanus

“…Within the last few years, select venoms in this clade have been characterized allowing inference of the presence and distribution of gene families that are expressed in venom. Venomic sampling to date includes venoms of Plectreurys tristis (Zobel-Thropp et al, 2014a), Scytodes thoracica (Zobel-Thropp et al, 2014b), and venoms within the family Sicariidae that includes brown recluse spiders (review in Chaves-Moreira et al, 2017). Adding a representative pholcid venom to this comparative set allows inference about the phylogenetic distribution and relative abundance of widespread gene families that contribute to spider venoms.…”