| Author | Cruz, Mariza Gabriela Faleiro de Moura Lodi | |
| Author | Santi, Ana Maria Murta | |
| Author | Teixeira, Eliane de Morais | |
| Author | Caldeira, Alisson Samuel Portes | |
| Author | Siqueira Filho, Ezequias Pessoa de | |
| Author | Oliveira, Edward José | |
| Author | Alves, Tânia Maria de Almeida | |
| Author | Murta, Silvane Maria Fonseca | |
| Access date | 2024-02-16T18:23:06Z | |
| Available date | 2024-02-16T18:23:06Z | |
| Document date | 2024 | |
| Citation | CRUZ, Mariza Gabriela Faleiro de Moura Lodi et al. Anti-Leishmania compounds can be screened using Leishmania spp. expressing red fluorescence (tdTomato). Antimicrobial Agents and Chemotherapy, v. 68, n. 1, p. 1-21, Jan. 2024. | en_US |
| ISSN | 0066-4804 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/62656 | |
| Language | eng | en_US |
| Publisher | ASM Journals | en_US |
| Rights | restricted access | |
| Title | Anti-Leishmania compounds can be screened using Leishmania spp. expressing red fluorescence (tdTomato) | en_US |
| Type | Article | |
| DOI | 10.1128/aac.00509-23 | |
| Abstract | The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated Leishmania braziliensis (Lb) and Leishmania infantum (Li) that constitutively express the tandem tomato red fluorescent protein ( tdTomato ) as a model for large-scale screens of anti- Leishmania compounds. Confocal microscopy of Lb and Li::tdTomato revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing tdTomato , their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine in vitro . The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of tdTomato did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with Lb and Li::tdTomato mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against L. braziliensis and L. infantum in vitro and in vivo . Our method could also enhance the discovery of active compounds for treating leishmaniasis. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Instituto René Rachou. Química de Produtos Naturais Bioativos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Química de Produtos Naturais Bioativos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Química de Produtos Naturais Bioativos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Química de Produtos Naturais Bioativos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Subject | Infectious Diseases | en_US |
| Subject | Pharmacology | en_US |
| Subject | Anti-Leishmania | en_US |
| Subject | Leishmaniasis chemotherapy | |
| Embargo date | 3100-12-31 | |
