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Master's Dissertation
DOI
10.11606/D.5.2008.tde-25032009-093612
Document
Author
Full name
Luciana Aparecida Camizotti
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Cotrim, Paulo Cesar (President)
Chioccola, Vera Lucia Pereira
Hoffmann, Erika Hellena Esther
Title in Portuguese
Identificação e caracterização cromossomal de 9 loci de Leishmania (L.) major relacionados com resistência a inibidores da via de biossíntese do ergosterol
Keywords in Portuguese
Ergosterol/antagonistas & inibidores
Ergosterol/biossíntese
Expressão gênica
Leishmania major
Resistência a medicamentos
Abstract in Portuguese
O ergosterol é um componente responsável por manter a integridade e a fluidez das membranas de Leishmania spp. A partir de uma metodologia que consiste em seleção por superexpressão gênica, foram isolados nove diferentes loci de L. (L.) major relacionados com a resistência a dois inibidores da via de biossíntese do ergosterol: Terbinafina (TBF) e Itraconazol (ITZ). Análises funcionais individuais desses nove loci na presença de TBF e ITZ (ou do análogo Cetoconazol - CTZ) apresentaram níveis significantes de resistência após transfecção em células selvagens de L. (L.) major. Nesse trabalho apresentamos a metodologia de isolamento de um desses loci (cItz2), bem como a análise in silico das regiões cromossômicas correspondentes aos insertos dos nove cosmídios no genoma de L. (L.) major
Title in English
Identification and chromosomal localization of 9 Leishmania (L.) major loci related to resistance against two inhibitors of ergosterol biosynthesis pathway
Keywords in English
Drug resistance
Ergosterol/antagonists & inhibitors
Ergosterol/biosynthesis
Gene expression
Leishmania major
Abstract in English
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 nine different loci of L. (L.) major related to resistance against two inhibitors of the ergosterol biosynthesis pathway, Terbinafine (TBF) and Itraconazole (ITZ). Individual functional analysis of these nine loci in the presence of TBF and/or ITZ (or the ITZ analog Ketoconazole, CTZ), have showed significant levels of resistance after transfection into L. (L.) major wild-type cells, followed by over expression induction. In this work, we show the insert mapping and chromosomal identification of one of these loci (cItz2), as well as discuss the in silico chromosomal analysis of the nine correspondent inserts in the L. (L.) major genome
 
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Publishing Date
2009-04-06
 
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