期刊
MEMORIAS DO INSTITUTO OSWALDO CRUZ
卷 107, 期 3, 页码 416-419出版社
FUNDACO OSWALDO CRUZ
DOI: 10.1590/S0074-02762012000300018
关键词
drug resistance; azoles; ergosterol biosynthesis
资金
- FIOCRUZ
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 mu M] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 mu M) and La10 (IC50 = 10 mu M). 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.
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