Brown Spider Venom Toxins: Biological Activities, Molecular Mechanisms, Cell Biology, Biotechnological Applications, and Targets for the Therapeutic Management of Loxoscelism

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 2526

Special Issue Editors


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Guest Editor
Department of Cell Biology, Federal University of Parana (Universidade Federal do Paraná-UFPR), Centro Politécnico, Curitiba CEP 81.531-980, PR, Brazil
Interests: animal venoms; protein toxins; molecular biology; cell biology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Cell Biology, Federal University of Parana (Universidade Federal do Paraná—UFPR), Centro Politécnico, Curitiba CEP 81.531-980, PR, Brazil
Interests: animal venoms; protein toxins; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brown spider venoms primarily consist of protein toxins used for predation and defense, which may act synergistically when present in tissue. Some of these toxins, such as phospholipases D, have already been recombinantly produced and extensively studied, demonstrating a pivotal role in the development of clinical manifestations following a Loxosceles bite. Other toxins, including hyaluronidases, allergen factors, serpin, TCTP, and knottins (ICK peptides), have also been identified and produced as recombinant proteins. Comprehensive data on their biochemical and biological activities have been elucidated, revealing numerous potential applications, although much information is still to be uncovered. The interest in the potential applications of brown spider toxins has been steadily increasing  in the biotechnological and pharmaceutical fields, as therapeutic targets for managing patients affected by brown spider bites. This Special Issue is dedicated to consolidating all these scattered pieces of information and introducing new findings regarding these remarkable toxins. We welcome reviews, communications, and articles presenting novel data on biological activities, molecular mechanisms, cell biology and promising applications of these molecules.

Prof. Dr. Luiza Helena Gremski
Prof. Dr. Sílvio Sanches Veiga
Guest Editors

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Keywords

  • Loxosceles
  • brown spider
  • venom
  • phospholipase D
  • sphingomyelinase D
  • hyaluronidase
  • knottin
  • serpin
  • TCTP

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Published Papers (2 papers)

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Research

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14 pages, 3562 KiB  
Article
Venom from Loxosceles Spiders Collected in Southeastern and Northeastern Brazilian Regions Cause Hemotoxic Effects on Human Blood Components
by Rafaela Silva-Magalhães, Ayla Mel Gomes dos Santos, Ana Luiza Silva-Araújo, Pamella Luize Peres-Damásio, Valéria Gonçalves de Alvarenga, Luciana Souza de Oliveira, Eladio Flores Sanchez, Carlos Chávez-Olórtegui, Luana Silveira da Rocha Nowicki Varela, Ana Luiza Bittencourt Paiva and Clara Guerra-Duarte
Toxins 2024, 16(12), 532; https://doi.org/10.3390/toxins16120532 - 10 Dec 2024
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Abstract
Spiders of the genus Loxosceles represent a public health problem in Brazil due to the severity of the cutaneous and systemic effects that may result from their bite. In the systemic form of loxoscelism, hemolytic anemia, thrombocytopenia, and disseminated intravascular coagulation can occur. [...] Read more.
Spiders of the genus Loxosceles represent a public health problem in Brazil due to the severity of the cutaneous and systemic effects that may result from their bite. In the systemic form of loxoscelism, hemolytic anemia, thrombocytopenia, and disseminated intravascular coagulation can occur. Despite the seriousness of Loxosceles accidents, the venom of some species has not yet been properly characterized considering these hemotoxic effects, such as that of Loxosceles amazonica, Loxosceles aff. Variegata, and Loxosceles similis. To better understand their toxic potential, this study aimed to characterize the hematotoxic properties of these Loxosceles venoms. The crude venom was obtained from specimens of L. amazonica, L. aff. Variegata, and L. similis available from Funed’s arachnidary. In washed platelets, L. aff. variegata inhibited platelet aggregation induced by collagen and convulxin, whereas L. amazonica and L. similis venoms were able to induce platelet aggregation. In the in vitro hemolysis assays, all venoms experimentally induced direct hemolysis of human erythrocytes in a concentration-dependent manner, with different intensities. Furthermore, evidence suggest that the ABO and Rh systems may influence hemolytic activity. Finally, the studied Loxosceles venoms degraded fibrinogen, suggesting possible alterations in the coagulation cascade. Based in the here-presented preliminary study, in vivo assays in model animals are needed to verify the real toxic potential of these species’ venom, building up knowledge to elucidate the action of Loxosceles venoms in blood. Full article
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Review

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21 pages, 3710 KiB  
Review
Brown Spider Venom Phospholipases D: From Potent Molecules Involved in Pathogenesis of Brown Spider Bites to Molecular Tools for Studying Ectosomes, Ectocytosis, and Its Applications
by Ana Carolina Martins Wille, Mariana Izabele Machado, Samira Hajjar Souza, Hanna Câmara da Justa, Maria Eduarda de Fraga-Ferreira, Eloise de Souza Mello, Luiza Helena Gremski and Silvio Sanches Veiga
Toxins 2025, 17(2), 70; https://doi.org/10.3390/toxins17020070 - 5 Feb 2025
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Abstract
Accidents caused by Loxosceles spiders, commonly known as brown spiders, are frequent in warm and temperate regions worldwide, with a higher prevalence in South America and the southern United States. In the venoms of species clinically associated with accidents, phospholipases D (PLDs) are [...] Read more.
Accidents caused by Loxosceles spiders, commonly known as brown spiders, are frequent in warm and temperate regions worldwide, with a higher prevalence in South America and the southern United States. In the venoms of species clinically associated with accidents, phospholipases D (PLDs) are the most expressed toxins. This classification is based on the toxins’ ability to cleave various phospholipids, with a preference for sphingomyelin. Studies using purified PLDs have demonstrated that these enzymes cleave phospholipids from cells, producing derivatives that can activate leukocytes. A dysregulated inflammatory response is the primary effect following envenomation, leading to dermonecrosis, which is histopathologically characterized by aseptic coagulative necrosis—a key feature of envenomation. Although advances in understanding the structure–function relationship of enzymes have been achieved through molecular biology, heterologous expression, site-directed mutations, crystallography, and bioinformatic analyses—describing PLDs in the venoms of various species and highlighting the conservation of amino acid residues involved in catalysis, substrate binding, and magnesium stabilization—little is known about the cellular biology of these PLDs. Studies have shown that the treatment of various cells with recombinant PLDs stimulates the formation of ectosomes and ectocytosis, events that initiate a cascade of intracellular signaling in PLD-binding cells and lead to the release of extracellular microvesicles. These microvesicles may act as signalosomes for other target cells, thereby triggering an inflammatory response and dermonecrosis. In this review, we will discuss the biochemical properties of PLDs, the target cells that bind to them, and the ectocytosis-dependent pathophysiology of envenoming. Full article
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