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
相关论文
共 59 条
[41]  
Ouellette M, 1998, METHOD ENZYMOL, V292, P182
[42]   DIRECT AND INVERTED DNA REPEATS ASSOCIATED WITH P-GLYCOPROTEIN GENE AMPLIFICATION IN DRUG-RESISTANT LEISHMANIA [J].
OUELLETTE, M ;
HETTEMA, E ;
WUST, D ;
FASEFOWLER, F ;
BORST, P .
EMBO JOURNAL, 1991, 10 (04) :1009-1016
[43]   IMPROVED TOOLS FOR BIOLOGICAL SEQUENCE COMPARISON [J].
PEARSON, WR ;
LIPMAN, DJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (08) :2444-2448
[44]   Characterization of LST-R533:: Uncovering a novel repetitive element in Leishmania [J].
Pedrosa, AL ;
Silva, AM ;
Ruiz, JC ;
Cruz, AK .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2006, 36 (02) :211-217
[45]   Cloning of S-adenosyl-L-Methionine:: C-24-Δ-sterol-methyltransferase (ERG6) from Leishmania donovani and characterization of mRNAs in wild-type and amphotericin B-resistant promastigotes [J].
Pourshafie, M ;
Morand, S ;
Virion, A ;
Rakotomanga, M ;
Dupuy, C ;
Loiseau, PM .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (07) :2409-2414
[46]   Resistance to antimony and treatment failure in human Leishmania (Viannia) infection [J].
Rojas, R ;
Valderrama, L ;
Valderrama, M ;
Varona, MX ;
Ouellette, M ;
Saravia, NG .
JOURNAL OF INFECTIOUS DISEASES, 2006, 193 (10) :1375-1383
[47]  
Romero Gustavo A. S., 2001, Clinical Infectious Diseases, V32, P1304, DOI 10.1086/319990
[48]  
Sambrook J., 1989, MOL CLONING LAB MANU, V2nd ed.
[49]   The 245 kb amplified chromosome of Leishmania (V.) braziliensis contains a biopterin transporter gene [J].
Sampaio, MCR ;
Traub-Cseko, YM .
MEMORIAS DO INSTITUTO OSWALDO CRUZ, 2003, 98 (03) :377-378
[50]   GENE AMPLIFICATION [J].
STARK, GR ;
WAHL, GM .
ANNUAL REVIEW OF BIOCHEMISTRY, 1984, 53 :447-491