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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 10, n. 5 MAY 2016.
• Web of Science Citations: 4

Abstract

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)

• FAPESP's process: 15/05130-5 - Characterization of Leishmania (v.) braziliensis clinical isolates susceptibility to miltefosine in vitro and in vivo
• Grantee: Caroline Ricce Espada
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 12/14629-5 - Mechanisms of action and resistance to miltefosine in Leishmania spp.
• Grantee: Adriano Cappellazzo Coelho
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/09080-2 - Evaluation of candidate drugs for the treatment of Leishmaniasis in Brazil
• Grantee: Silvia Reni Bortolin Uliana
• Support type: Regular Research Grants
• FAPESP's process: 11/18858-6 - TAMOXIFEN AS AN ANTI-LEISHMANIAL DRUG: ACTIVITY IN COMBINED THERAPEUTIC SCHEMES AND STUDY OF THE MECHANISM OF ACTION
• Grantee: Cristiana de Melo Trinconi Tronco
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/20484-7 - Tamoxifen in the treatment of leishmaniasis: evaluation of efficacy in combination therapy schemes and study of the antileishmanial mechanism of action
• Grantee: Silvia Reni Bortolin Uliana
• Support type: Regular Research Grants