A Luciferase-Expressing Leishmania braziliensis Line That Leads to Sustained Skin Lesions in BALB/c Mice and Allows Monitoring of Miltefosine Treatment Outcome

Autor(es)

Coelho, Adriano C. ^{[1, 2]} ; Oliveira, Jordana C. ^[1] ; Espada, Caroline R. ^[1] ; Reimao, Juliana Q. ^{[1, 3]} ; Trinconi, Cristiana T. ^[1] ; Uliana, Silvia R. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Biol Anim, Campinas, SP - Brazil

^[3] Fac Med Jundiai, Dept Morfol & Patol Basica, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 10, n. 5 MAY 2016.
• Citações Web of Science: 4

Resumo

Background Leishmania braziliensis is the most prevalent species isolated from patients displaying cutaneous and muco-cutaneous leishmaniasis in South America. However, there are difficulties for studying L. braziliensis pathogenesis or response to chemotherapy in vivo due to the natural resistance of most mouse strains to infection with these parasites. The aim of this work was to develop an experimental set up that could be used to assess drug efficacy against L. braziliensis. The model was tested using miltefosine. Methodology/Principal Findings A L. braziliensis line, originally isolated from a cutaneous leishmaniasis patient, was passaged repeatedly in laboratory rodents and further genetically manipulated to express luciferase. Once collected from a culture of parasites freshly transformed from amastigotes, 10(6) wild type or luciferase-expressing stationary phase promastigotes were inoculated subcutaneously in young BALB/c mice or golden hamsters. In both groups, sustained cutaneous lesions developed at the site of inoculation, no spontaneous self-healing being observed 4 months post-inoculation, if left untreated. Compared to the wild type line features, no difference was noted for the luciferase-transgenic line. Infected animals were treated with 5 or 15 mg/kg/day miltefosine orally for 15 days. At the end of treatment, lesions had regressed and parasites were not detected. However, relapses were observed in animals treated with both doses of miltefosine. Conclusions/Significance Here we described experimental settings for a late-healing model of cutaneous leishmaniasis upon inoculation of a luciferase-expressing L. braziliensis line that can be applied to drug development projects. These settings allowed the monitoring of the transient efficacy of a short-term miltefosine administration. (AU)

• Processo FAPESP: 15/05130-5 - Caracterização da suscetibilidade de isolados clínicos de Leishmania (Viannia) braziliensis à miltefosina in vitro e in vivo
• Beneficiário: Caroline Ricce Espada
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/18858-6 - Tamoxifeno como droga anti-leishmania: atividade em esquemas terapêuticos combinados e estudo do mecanismo de ação
• Beneficiário: Cristiana de Melo Trinconi Tronco
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/14629-5 - Mecanismos de ação e resistência à Miltefosina Leishmania spp.
• Beneficiário: Adriano Cappellazzo Coelho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/09080-2 - Avaliação de candidatos a fármacos para o tratamento de leishmaniose no Brasil
• Beneficiário: Silvia Reni Bortolin Uliana
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/20484-7 - Tamoxifeno no tratamento de leishmaniose: avaliação de eficácia em esquemas de combinação de drogas e estudo do mecanismo de ação
• Beneficiário: Silvia Reni Bortolin Uliana
• Modalidade de apoio: Auxílio à Pesquisa - Regular