search
for
 About Bioline  All Journals  Testimonials  Membership  News  Donations


Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 107, No. 3, 2012, pp. 416-419
Bioline Code: oc12059
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 107, No. 3, 2012, pp. 416-419

 en The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis check for this species in other resources
Andrade-Neto, Valter Viana; de Matos-Guedes, Herbert Leonel; Gomes, Daniel Cláudio de Oliveira; do Canto-Cavalheiro, Marilene Marcuzzo; Rossi-Bergmann, Bartira & Torres-Santos, Eduardo Caio

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 check for this species in other resources 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

 
© Copyright 2012 - Memorias do Instituto Oswaldo Cruz
Alternative site location: http://memorias.ioc.fiocruz.br

Home Faq Resources Email Bioline
© Bioline International, 1989 - 2017, Site last up-dated on 16-Oct-2017.
Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil
System hosted by the Internet Data Center of Rede Nacional de Ensino e Pesquisa, RNP, Brazil