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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Camizotti, L. A. [1] ; Yamashiro-Kanashiro, E. H. [1] ; Cotrim, Paulo C. [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Inst Trop Med, Depto Molestias Infecciosas & Parasitarias, BR-05403000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Parasitology Research; v. 105, n. 2, p. 471-478, AUG 2009.
Web of Science Citations: 3
Abstract

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)