Identification and chromosomal localization of one locus of Leishmania (L.) major related with resistance to itraconazole

Autor(es)

Camizotti, L. A. ^[1] ; Yamashiro-Kanashiro, E. H. ^[1] ; Cotrim, Paulo C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Trop Med, Depto Molestias Infecciosas & Parasitarias, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Parasitology Research; v. 105, n. 2, p. 471-478, AUG 2009.
• Citações Web of Science: 3

Resumo

Ergosterol is an important compound responsible to maintain integrity and fluidity of Leishmania spp. membranes. Starting from an overexpression/selection method, our group has isolated and mapped nine different loci of Leishmania (L.) major related to resistance against two inhibitors of the ergosterol biosynthesis pathway, terbinafine (TBF) and itraconazole (ITZ). Individual functional analysis after overexpression induction of these loci in the presence of TBF and/or ITZ {[}or the ITZ analog ketoconazole (CTZ)] have shown low but significant levels of resistance after transfection into L. major wild-type parasites. In this work, we have shown the insert mapping and chromosomal identification of one of these loci (cosItz2). Functional analysis experiments associated with chromosomal localization by comparison at genomic database allowed us to identify two prospective gene-protein systems not related to the ergosterol biosynthesis and capable to confer wild-type cells resistance to ITZ-CTZ after transfection. We expected that this approach can open new insights for a better understanding of mechanisms of ITZ-CTZ action and resistance in Leishmania resulting in new strategies for the leishmaniasis treatment. (AU)

• Processo FAPESP: 02/09562-7 - Identificacao e analise de genes / loci de leishmania major relacionados com a resistencia a dois inibidores da biossintese do ergosterol.
• Beneficiário: Paulo Cesar Cotrim
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 00/10016-1 - Identificação de genes/loci de (Leishmania major) relacionados com a ação anti-parasitária do terbinafine e itraconazol
• Beneficiário: Debora Cristina da Costa Ramos
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 06/04656-4 - Papel do transportador abc prp1 de leishmania spp. na resistencia a pentamidina.
• Beneficiário: Paulo Cesar Cotrim
• Linha de fomento: Auxílio à Pesquisa - Regular