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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 6
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
Total Affiliations: 3
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