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.
Highlights
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
Response, necrosis and interstitial edema found in the histological analyses of rabbit skin exposed to II–V) corroborate with those previous studies and agree with the histopathological changes triggered by a L. intermedia PLD (Figure 1G II–V) corroborate with those previous studies and agree with the the whole venom
Phospholipase D of Loxosceles gaucho. (I) Cartoon representation of the structures of Brown spider venom PLDs: structural features highlighted in green, cyan and orange are from Loxosceles intermedia (PDB code: 3RLH) and in red are from Loxosceles laeta (PDB code: 1XX1)
Summary
Loxoscelism, the set of clinical manifestations of envenomation by Brown Spiders (Loxosceles genus), can be cutaneous and systemic. Unlike animals of control group, insects that received recombinant PLD were paralyzed 15 min after exposition (turned upside down in images), and no recovery was observed These crickets were dead within 24 h. Toxins 2020, 12, x FOR PEER REVIEW response, necrosis and interstitial edema found in the histological analyses of rabbit skin exposed to II–V) corroborate with those previous studies and agree with the histopathological changes triggered by a L. intermedia PLD (Figure 1G II–V) corroborate with those previous studies and agree with the the whole venom [17]. (I) Cartoon representation of the structures of Brown spider venom PLDs: structural features highlighted in green, cyan and orange (catalytic, flexible, and variable loops, respectively) are from Loxosceles intermedia (PDB code: 3RLH) and in red are from Loxosceles laeta (PDB code: 1XX1). Ethics Committee for Animal Studies Guidelines from Federal University of Paraná (Certificate n◦ 1112 of the Federal University of Paraná)
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