Molecular architecture of black widow spider neurotoxins.

Latrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders. The venom contains a toxic cocktail of seven LaTXs, with one of them targeting vertebrates (α-latrotoxin (α-LTX)), five specialized on insects (α, ß, γ, δ, ε- latroinsectotoxins (LITs), and one on crustaceans (α-latrocrustatoxin (α-LCT)). LaTXs bind to specific receptors on the surface of neuronal cells, inducing the release of neurotransmitters either by directly stimulating exocytosis or by forming Ca2+-conductive tetrameric pores in the membrane. Despite extensive studies in the past decades, a high-resolution structure of a LaTX is not yet available and the precise mechanism of LaTX action remains unclear. Here, we report cryoEM structures of the α-LCT monomer and the δ-LIT dimer. The structures reveal that LaTXs are organized in four domains. A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. Both domains are flexibly linked via an N-terminal α-helical domain and a small ß-sheet domain. A comparison between the structures suggests that oligomerization involves major conformational changes in LaTXs with longer C-terminal domains. Based on our data we propose a cyclic mechanism of oligomerization, taking place prior membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions and allow calcium flux at negative membrane potentials. Our comparative analysis between α-LCT and δ-LIT provides first crucial insights towards understanding the molecular mechanism of the LaTX family.

A Review of Black Widow (Araneae: Theridiidae) Envenomation, Epidemiology, and Antivenom Utilization in Canada.

Two species of black widow spider (BWS-Latrodectus hesperus Chamberlin & Ivie and Latrodectus variolus Walckenaer) naturally occur in Canada and are capable of causing deleterious envenomation to humans. No Canadian literature exists on the frequency of envenomations by these species or the use of antivenom in the treatment of those patients. A review of primary Canadian arachnology data was undertaken to identify BWS populations. A retrospective review of the Health Canada Special Access Program records generated epidemiology and the utilization of antivenom for BWS envenomations in Canada. The geographical distribution of BWS species is limited to along the southern Canadian border. From January 2009 to December 2015, there were five BWS envenomations that required treatment with antivenom and all cases occurred in British Columbia. An average patient age of 41 yr ± 21 SD (range 7-59) was observed, along with three of the five patients being female. The average number of vials used for treatment was 2 ± 1 SD (range 1-3). BWS Antivenin was also obtained by facilities in Alberta, Ontario, and Nova Scotia, but not used in any of these jurisdictions. Further investigation is necessary to determine the annual incidence of BWS envenomations and if treatment with BWS antivenin is required.

Latrodectus Facies After Latrodectus Hesperus Envenomation in a Pediatric Patient.

BACKGROUND: Black widow spider (Latrodectus spp) envenomation represents the most medically significant spider envenomation in the United States, prompting more than 2500 calls to poison centers annually. The female spider, which is responsible for symptomatic envenomations, is classically described as a shiny black spider with a red hourglass-shaped marking on the ventral abdomen. Clinical features of envenomation include painful muscle cramping, abdominal pain, and autonomic disturbances, such as tachycardia, hypertension, and diaphoresis. "Latrodectus facies" or "facies latrodectismica" is an additional distinctive but rarely described clinical finding characterized by periorbital edema, lacrimation, and blepharospasm. CASE REPORT: A 6-year-old female developed the typical clinical features of Latrodectus envenomation after being found in bed with a Western black widow spider (Latrodectus hesperus) with no ventral marking. She initially improved with opioid analgesia, but 6 h later her symptoms worsened again, and concurrent with this worsening she developed Latrodectus facies. She received additional opioid analgesia and all her symptoms resolved within 24 h. Her mother provided informed and written consent for the acquisition and publication of the facial photographs presented. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A high degree of clinical suspicion is necessary to correctly diagnose Latrodectus envenomation, especially when the spider escapes unnoticed or in young children in whom the bite is not witnessed. To our knowledge, Latrodectus facies has not been reported previously in a young child, and recognition of this finding will aid clinicians in limiting unnecessary interventions and administering appropriate therapy.

Manifestaciones de neurotoxicidad en el envenenamiento por mordedura de araña «viuda negra» en edades pediátricas / Neurotoxic manifestations of black widow spider envenomation in paediatric patients

Introducción: El envenenamiento por mordedura de araña «viuda negra» (Latrodectus mactans) en niños se expresa clínicamente con neurotoxicidad. Objetivo: Identificar los signos y síntomas neurológicos característicos, en las diferentes edades pediátricas, la evolución y el tratamiento en pacientes atendidos por esta mordedura de en un hospital pediátrico de noroeste México. Material y métodos: Se revisaron 70 expedientes de niños hospitalizados entre 1978-2014; estableciéndose 2 grupos: grupo 1, de 33 lactantes y preescolares, y grupo 2, con 37 escolares y adolescentes. Las variables consideradas fueron: edad, género, lugar de procedencia, sitio del accidente, área corporal afectada, grado de envenenamiento, tratamiento, evolución clínica, diferencias estadísticas. Resultados: Predominó el género masculino, 61,4%; los lactantes menores de un año fueron un 14,2%. El 70% de los pacientes tuvieron el contacto con el arácnido dentro del domicilio; las áreas anatómicas más afectadas fueron miembros inferiores, cuello, tronco y abdomen; los signos y síntomas neurológicos más notables en el grupo 1 fueron: irritabilidad, llanto constante, naáseas, sialorrea, agitación, taquicardia, arritmias, incapacidad para caminar, espasmos musculares, parestesias, tetania, convulsiones, nistagmo. En el grupo 2 fueron: dolor local, cefalea, sialorrea, parestesias, sudoración profusa, ansiedad, debilidad muscular, espasmos musculares y temblor fino. La manifestación clínica autonómicas predominante en el grupo 1 fue sialorrea, p < 0,0001, y en el grupo 2, parestesias, p < 0,0001. El uso de faboterápicos en el tratamiento permitió mejor evolución, menor tiempo de hospitalización, no hubo mortalidad. Conclusiones: Los signos y los síntomas de la mordedura por araña «viuda negra» son predominantemente autonómicos; identificarlos permite el diagnóstico oportuno y tratamiento eficaz

Introduction: Envenomation by black widow spiders manifests clinically with signs of neurotoxicity in paediatric patients. Objective: Identify typical neurological signs and symptoms in paediatric patients of different ages, and describe treatment and outcomes in a paediatric hospital in northwest Mexico. Material and methods: We reviewed 70 clinical records of patients hospitalised due to black widow spider bite between 1978 and 2014. We divided the total into 2 groups: Group 1, infants and preschool children; and Group 2, school-age children and adolescents. The demographic variables were age, sex, birthplace, place where envenomation occurred, body part(s) affected, degree of envenomation according to signs and symptoms, treatment, clinical outcome, and statistical differences. Results: Boys accounted for 61.4% of all cases, and infants younger than one year old made up 14.2%. Most patients (70%) were bitten by the spider at home; the anatomical areas most frequently affected were the legs, neck, thorax, and abdomen. The neurological signs and symptoms displayed by Group 1 were irritability, constant crying, sialorrhoea, nausea, tachycardia, arrhythmias, fatigue when walking, agitation, muscle spasms paraesthesia, tetany, seizures, and nystagmus. Signs in Group 2 included localized pain, headache, sialorrhoea, paraesthesia, profuse sweating, anxiety, muscle weakness, muscle spasms, and fine tremor. The predominant autonomic sign in Group 1 was sialorrhoea (P<.0001) and in Group 2, paraesthesia (P<.0001). Patients who received Fab antivenom treatment displayed better outcomes and shorter hospital stays than those who did not. No deaths were reported. Conclusions: The neurological signs and symptoms caused by black widow spider bite are predominantly autonomic, and identifying them permits early diagnosis and more effective treatment

Protein compositional analysis of the eggs of black widow spider (Latrodectus tredecimguttatus): implications for the understanding of egg toxicity.

Previous work found that high-molecular-weight fractions in the egg extract of Latrodectus tredecimguttatus exhibited strong toxicities. For investigating the possible relationship of proteins in the eggs with the toxic effect, the protein composition of the eggs was analyzed using proteomic strategies and compared with that of the spider's venom. SDS-PAGE showed that the proteins of eggs were primarily distributed in the molecular weight range of higher than 55 kDa as well as around 34 kDa, having high abundance proteins with molecular weights of about 60 kDa and 130 kDa. A total of 157 proteins were identified from the egg extract, which were involved in important cellular functions and processes including catalysis, transport, and metabolism regulation. Comparison indicated that the protein composition of eggs is more complex than that of venom, and there are few similarities between the protein composition of the two materials, demonstrating that the eggs have their own distinct toxic mechanism.

Molecular characterization, electrophysiological and contraceptive effect of chilean latrodectus venom / Caracterización molecular, electrofisiológica y efecto anticonceptivo del veneno de latrodectus chilena

Since the 1970s, There have been studies of the venom of Latrodectus sp. spiders, in particular the latrotoxin (LTX) of Latrodectus mactans. Many of the studies were aimed at understanding the action of the venom on the muscular system. Now accepted that LTX is able to generate a calcium-permeable membrane pore and modulate the release of synaptic vesicles that activate a receptor and induce cellular changes. Interestingly, when work began with venom obtained from the Latrodectus sp present in Chile, it generated clinical indications similar to the bite of this spider in another country, with some differences in intensity. The purpose of the first studies was to understand the systemic mechanisms of this venom, and other active compounds were studied for biological interest. It was found that these molecules are capable of causing systemic effects such as changes in muscle contraction; of generating vascular relaxation and synaptic and cellular modulation; and of altering potassium conductance channels. Based on this evidence, we suggested biotechnological applications to characterize low molecular-weight compounds obtained from the Chilean Latrodectus venom and exploring the effects on the electrophysiology in oocytes and neurons, and the contraceptive effect on spermatozoa.

Desde los años 70, se han realizado estudios con el veneno de arañas Latrodectus sp, en particular la latrotoxina (LTX) de Latrodectus mactans. Muchos de estos estudios estuvieron enfocados a entender la acción del veneno sobre el sistema muscular. Hoy en día es aceptado que la LTX es capaz de generar un poro de membrana permeable a calcio y modular la liberación de vesículas sinápticas que activan un receptor e inducen cambios celulares. Interesantemente, cuando comenzamos a trabajar con el veneno obtenido de Latrodectus sp. presente en Chile, ésto generó indicaciones clínicas similares a la picadura de esta araña en otros países, con algunas diferencias en su intensidad. El propósito de estos primeros estudios fue entender los mecanismos sistémicos de este veneno y además otros compuestos activos fueron estudiados para interés biológico. Se ha encontrado que estas moléculas son capaces de causar efectos sistémicos así como cambios en la contracción muscular; generar relajación vascular y modulación sináptica y celular; y de alterar los canales de conductancia de potasio. Basados en estas evidencias, nosotros sugerimos usar aplicaciones biotecnológicas para caracterizar los compuestos de bajo peso molecular obtenidos del veneno de Latrodectus Chilena y explorar los efectos sobre la electrofisiología en ovocitos y neuronas, y el efecto anticonceptivo sobre los espermatozoides.

Latrodectismo / Latrodectism

Numerosas especies de artrópodos poseen veneno capaz de producir enfermedad en el ser humano. Por su severidad y frecuencia, debe destacarse la causa por arácnidos (aracnidismo), especialmente la producida por el género Latrodectus (Orden Araneida), capaz de desencadenar un cuadro neurotóxico grave, denominado latrodectismo. En este artículo se revisan los aspectos biológicos, clínicos y terapéuticos más relevantes de esta patología

Latrodectismo: 67 casos; Hospital Galvarino IX Región / Latrodectism: 67 cases; Hospital Galvarino IX Región

Revisión retrospectiva y descriptiva de 67 casos de mordedura por latrodectus manctans ocurridos en 7 periódos estivales (1983-1990) en el Hospital de Galvarino, IX Región, Chile. Se confirma predominio de incidencia en varones jóvenes que desarrollan faenas agrícolas en horario diurno. Cuadro clínico con predominio de las manifestaciones tóxicas generales. El tratamiento sintomático con dipirona y neostigmina tiene éxito en 90 por ciento con alta al 4§ día. Se confirma correlación lineal negativa (r=0,801) entre cantidad de H2O caída en primavera y número de casos con mordedura en verano