title: Recent advances in the understanding of brown spider venoms: From the biology of spiders to the molecular mechanisms of toxins.
abstract: The Loxosceles genus spiders (the brown spiders) are encountered in all the continents, and the clinical manifestations following spider bites include skin necrosis with gravitational lesion spreading and occasional systemic manifestations, such as intravascular hemolysis, thrombocytopenia and acute renal failure. Brown spider venoms are complex mixtures of toxins especially enriched in three molecular families: the phospholipases D, astacin-like metalloproteases and Inhibitor Cystine Knot (ICK) peptides. Other toxins with low level of expression also present in the venom include the serine proteases, serine protease inhibitors, hyaluronidases, allergen factors and translationally controlled tumor protein (TCTP). The mechanisms by which the Loxosceles venoms act and exert their noxious effects are not fully understood. Except for the brown spider venom phospholipase D, which causes dermonecrosis, hemolysis, thrombocytopenia and renal failure, the pathological activities of the other venom toxins remain unclear. The objective of the present review is to provide insights into the brown spider venoms and loxoscelism based on recent results. These insights include the biology of brown spiders, the clinical features of loxoscelism and the diagnosis and therapy of brown spider bites. Regarding the brown spider venom, this review includes a description of the novel toxins revealed by molecular biology and proteomics techniques, the data regarding three-dimensional toxin structures, and the mechanism of action of these molecules. Finally, the biotechnological applications of the venom components, especially for those toxins reported as recombinant molecules, and the challenges for future study are discussed.
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil; Departamento de Patologia Clínica, Hospital de Clínicas, Universidade Federal do Paraná, Brazil.
authors.forename: Luiza Helena
authors.initials: LH
authors.lastname: Gremski
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Dilza
authors.initials: D
authors.lastname: Trevisan-Silva
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Valéria Pereira
authors.initials: VP
authors.lastname: Ferrer
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Fernando Hitomi
authors.initials: FH
authors.lastname: Matsubara
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Gabriel Otto
authors.initials: GO
authors.lastname: Meissner
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil; Departamento de Biologia Estrutural, Molecular e Genética, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil.
authors.forename: Ana Carolina Martins
authors.initials: AC
authors.lastname: Wille
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Vuitika
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Dias-Lopes
authors.affiliation: Centro Multiusuário de Inovação Biomolecular, Departamento de Física, Universidade Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Anwar
authors.initials: A
authors.lastname: Ullah
authors.affiliation: Centro Multiusuário de Inovação Biomolecular, Departamento de Física, Universidade Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Fábio Rogério
authors.initials: FR
authors.lastname: de Moraes
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chávez-Olórtegui
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Katia Cristina
authors.initials: KC
authors.lastname: Barbaro
authors.affiliation: Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil.
authors.forename: Mario Tyago
authors.initials: MT
authors.lastname: Murakami
authors.affiliation: Centro Multiusuário de Inovação Biomolecular, Departamento de Física, Universidade Estadual Paulista (UNESP), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Raghuvir Krishnaswamy
authors.initials: RK
authors.lastname: Arni
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Senff-Ribeiro
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Olga Meiri
authors.initials: OM
authors.lastname: Chaim
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: veigass@ufpr.br.
authors.forename: Silvio Sanches
authors.initials: SS
authors.lastname: Veiga
mesh_terms: D000818:Animals; D000997:Antivenins / Q000737:chemistry; D060829:Arthropod Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D008297:Male; D008958:Models, Molecular; D010739:Phospholipase D / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D040901:Proteomics; D057057:Serine Proteases / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D001098:Spider Bites / Q000473:pathology; D013111:Spider Venoms / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D013112:Spiders / Q000033:anatomy & histology / Q000737:chemistry* / Q000502:physiology; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D000997:Antivenins; D060829:Arthropod Proteins; D014408:Biomarkers, Tumor; D013111:Spider Venoms; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D010739:Phospholipase D; D006821:Hyaluronoglucosaminidase; D057057:Serine Proteases
keywords: Brown spider; Dermonecrosis; Loxosceles; Loxoscelism; Toxins; Venom