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

Abstract

Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the enzyme also cleaved other cellular phospholipids. In this review, we present the information gleaned over the last 40 years about PLDs from Loxosceles venoms especially with regard to the production and characterization of recombinant isoforms. The history of obtaining these toxins is discussed, as well as their molecular organization and mechanisms of interaction with their substrates. We will address cellular biology aspects of these toxins and how they can be used in the development of drugs to address inflammatory processes and loxoscelism. Present and future aspects of loxoscelism diagnosis will be discussed, as well as their biotechnological applications and actions expected for the future in this field.

New Insectotoxin from Tibellus Oblongus Spider Venom Presents Novel Adaptation of ICK Fold

“…Spider venom is composed of proteins, including enzymes [ 1 , 2 ] and large toxins (e.g., α-latrotoxin from black widow spider venom, a powerful presynaptic secretagogue [ 3 ]), small peptides, and low molecular weight compounds [ 1 ]. Small peptides usually make up the majority of the venom and can be divided into linear (not containing intramolecular disulfide bonds) and disulfide-stabilized.…”

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

“…However, this was not the case for the recombinant Smase D LiD1 given that this specific toxin may not be the best representative of the Loxosceles (Loxtox) phospholipase D family targeted by LimAb7. Indeed, the Loxtox family has been extensively characterized and is comprised of a great amount of Smase D isoforms [6], with distinct biological activities (e.g., hemolytic and sphingomyelinase activities were not significant for LiD1, despite producing dermonecrosis in vivo) [53]. We also observed that the thermal stability of the molecule was not optimal and this may be a consequence of some of the mutations introduced.…”

“…As indicated by 2D electrophoresis, the protein content of the venom has great interspecies similarity, with proteins ranging from 2 to 94 kDa. This includes serine proteases, serine protease inhibitors, hyaluronidases, inhibitor cystine knot (ICK) peptides and phospholipases D (PLD), the latter being the most studied and well-characterized venom components due to their ability to induce dermonecrotic lesions and hemolysis [6]. More than 25 spots immunologically related to PLD toxins have been identified in the L. intermedia venom, most of them being SMase D-related [7].…”

Família e escola: Desafios e perspectivas para a gestão escolar

“…O loxocelismo pode gerar dois tipos de quadros clínicos distintos: o quadro cutâneo ou dermonecrótico em que ocorre uma reação inflamatória intensa no local da picada e após vários dias forma-se uma área de necrose com uma lesão circulada por halo vermelho, com uma zona pálida central, chamada de placa marmórea (FUTRELL, 1992) e o quadro cutâneo-visceral ou sistêmico no qual podem ser observados alterações no quadro hematológico, podendo chegar à coagulação intravascular disseminada, agregação plaquetária e anemia hemolítica. Em pacientes que foram a óbito pode ser ressaltado alterações degenerativas nos parênquimas de vários órgãos, entre elas se destacam edema, congestão, hemorragia e erosões da mucosa digestiva, além de lesões renais e insuficiência renal aguda (IRA) (da SILVA, et al, 2004GREMSKI et al, 2020.…”

“…As aranhas do gênero Loxosceles provocam um conjunto de sinais e sintomas nos acidentados denominado loxoscelismo que pode desencadear o quadro cutâneo ou dermonecrótico (maioria dos casos) e o quadro cutâneo-visceral ou sistêmico (GREMSKI, et al, 2020).…”