Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/19059
Title: The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis
Authors: Andrade Neto, Valter Viana
Guedes, Herbert Leonel de Matos
Gomes, Daniel Cláudio de Oliveira
Cavalheiro, Marilene Marcuzzo do Canto
Bergmann, Bartira Rossi
Santos, Eduardo Caio Torres
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Espírito Santo. Departamento de Patologia. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.
Abstract: Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)50 = 2 μM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 μM) and La10 (IC50 = 10 μM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance.
Keywords: drug resistance
azoles
ergosterol biosynthesis
Leishmania amazonensis
keywords: Resistência a medicamentos
Azóis
Ergosterol
Biossíntese
Leishmania
Issue Date: 2012
Publisher: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz
Citation: ANDRADE NETO, Valter Viana; et al. The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis. Mem Inst Oswaldo Cruz, v..107, n.3, p.416-419. May 2012.
ISSN: 0074-0276
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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