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

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Abstract

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.

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Acknowledgment

We thank Marlei J. Augusto for technical assistance. This work was supported by the CNPq; FAPESP, 04/03397-0 and UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases; FCD; WCZL and FMS were sponsored by FAPESP (04/15619-7; 05/02997-6; 01/02527-9). The L. braziliensis sequence data were produced by the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute and are available from the website http://www.sanger.ac.uk/Projects/L_braziliensis.

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  1. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, Sao Paulo, Brazil

    Fabricio C. Dias, Jeronimo C. Ruiz, Wilton C. Z. Lopes, Fabio M. Squina, Adriana Renzi, Angela K. Cruz & Luiz R. O. Tosi

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  1. Fabricio C. Dias
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  2. Jeronimo C. Ruiz
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Correspondence to Luiz R. O. Tosi.

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Dias, F.C., Ruiz, J.C., Lopes, W.C.Z. et al. Organization of H locus conserved repeats in Leishmania (Viannia) braziliensis correlates with lack of gene amplification and drug resistance. Parasitol Res 101, 667–676 (2007). https://doi.org/10.1007/s00436-007-0528-5

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