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

被引:17
作者
Dias, Fabricio C. [1 ]
Ruiz, Jeronimo C. [1 ]
Lopes, Wilton C. Z. [1 ]
Squina, Fabio M. [1 ]
Renzi, Adriana [1 ]
Cruz, Angela K. [1 ]
Tosi, Luiz R. O. [1 ]
机构
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagnetes Patogen, BR-14049900 Ribeirao Preto, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
D O I
10.1007/s00436-007-0528-5
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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.
引用
收藏
页码:667 / 676
页数:10
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