Organization of H locus conserved repeats in Leishmania (Viannia) braziliensis correlates with lack of gene amplification and drug resistance

Autor(es)

Dias, Fabricio C. ; Ruiz, Jeronimo C. ; Lopes, Wilton C. Z. ; Squina, Fabio M. ; Renzi, Adriana ; Cruz, Angela K. ^[6] ; Tosi, Luiz R. O.

• Tipo de documento: Artigo Científico
• Fonte: Parasitology Research; v. 101, n. 3, p. 667-676, Aug. 2007.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Assunto(s): Protozoa Leishmania braziliensis Ácidos nucleicos Meglumina Antimônio Metotrexato

Resumo

Resistance to antimonials is a major problem when treating visceral leishmaniasis in India and has already been described for New World parasites. Clinical response to meglumine antimoniate in patients infected with parasites of the Viannia sub-genus can be widely variable, suggesting the presence of mechanisms of drug resistance. In this work, we have compared L. major and L. braziliensis mutants selected in different drugs. The cross-resistance profiles of some cell lines resembled those of mutants bearing H locus amplicons. However, amplified episomal molecules were exclusively detected in L. major mutants. The analysis of the L. braziliensis H region revealed a strong conservation of gene synteny. The typical intergenic repeats that are believed to mediate the amplification of the H locus in species of the Leishmania sub-genus are partially conserved in the Viannia species. The conservation of these non-coding elements in equivalent positions in both species is indicative of their relevance within this locus. The absence of amplicons in L. braziliensis suggests that this species may not favour extra-chromosomal gene amplification as a source of phenotypic heterogeneity and fitness maintenance in changing environments. (AU)

• Processo FAPESP: 05/02997-6 - Caracterizacao dos mecanismos de resistencia a antimoniais elicitados em diferentes especies do parasita protozoario leishmania.
• Beneficiário: Wilton Carlos Zanetti Lopes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 04/03397-0 - Estudo de fenótipos associados ao locus H de Leishmania spp.: caracterização de genes desconhecidos, efeito da amplificação e sinergismo de genes
• Beneficiário: Luiz Ricardo Orsini Tosi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/15619-7 - Caracterizacao de mecanismos de resistencia a terbinafina em diferentes especies de leishmania.
• Beneficiário: Fabrício César Dias
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 01/02527-9 - Nocaute sistematico de genes em (leishmania major). utilizacao de sistema "mariner mos1" de transposicao "in vitro".
• Beneficiário: Fábio Márcio Squina
• Modalidade de apoio: Bolsas no Brasil - Doutorado