A protein of the leucine-rich repeats (LRRs) superfamily is implicated in antimony resistance in Leishmania infantum amastigotes

被引:14
作者
Genest, Paul-Andre
Haimeur, Anass
Legare, Danielle
Sereno, Denis
Roy, Gaetan
Messier, Nadine
Papadopoulou, Barbara
Ouellette, Marc
机构
[1] CHU Laval, Ctr Rech & Infect, Ctr Rech, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Fac Med, Dept Microbiol, Quebec City, PQ G1K 7P4, Canada
基金
加拿大健康研究院;
关键词
Leishmania amastigotes; functional cloning; drug resistance; leucine-rich repeats;
D O I
10.1016/j.molbiopara.2007.11.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pentavalent antimonial containing drugs (SbV) are the mainstay for the control of the protozoan parasite Leishmania but resistance to this class of drug is now prevalent in several endemic areas. We describe here the use of functional cloning where an expression cosmid bank derived from Leishmania infantum was transfected in L. infantum axenic amastigotes and selected for potassium antimonyl tartrate (SbIII) resistance. This strategy allowed the isolation of a cosmid encoding for a novel resistance protein, LinJ34.0570, which belongs to the superfamily of leucine-rich repeat (LRR) proteins. Parasites overexpressing this LRR protein, which is part of the LRR-CC subfamily, were resistant to SbIII as axenic amastigotes and to SbV as intracellular parasites. This work pinpoints a novel protein that can contribute to antimonial resistance in Leishmania. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:95 / 99
页数:5
相关论文
共 25 条
[1]   The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite Leishmania [J].
Brochu, C ;
Haimeur, A ;
Ouellette, M .
CELL STRESS & CHAPERONES, 2004, 9 (03) :294-303
[2]   Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major [J].
Coelho, AC ;
Beverley, SM ;
Cotrim, PC .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2003, 130 (02) :83-90
[3]   Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection [J].
Cotrim, PC ;
Garrity, LK ;
Beverley, SM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (53) :37723-37730
[4]   Drug resistance in leishmaniasis [J].
Croft, SL ;
Sundar, S ;
Fairlamb, AH .
CLINICAL MICROBIOLOGY REVIEWS, 2006, 19 (01) :111-+
[5]   Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal [J].
Decuypere, S ;
Rijal, S ;
Yardley, V ;
De Doncker, S ;
Laurent, T ;
Khanal, B ;
Chappuis, F ;
Dujardin, JC .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (11) :4616-4621
[6]   Structural principles of Leucine-Rich repeat (LRR) proteins [J].
Enkhbayar, P ;
Kamiya, M ;
Osaki, M ;
Matsumoto, T ;
Matsushima, N .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2004, 54 (03) :394-403
[7]   The leucine-rich repeat as a protein recognition motif [J].
Kobe, B ;
Kajava, AV .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2001, 11 (06) :725-732
[8]   Developmental regulation of spliced leader RNA gene in Leishmania donovani amastigotes is mediated by specific polyadenylation [J].
Lamontagne, J ;
Papadopoulou, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6602-6609
[9]   Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony [J].
Mandal, G. ;
Wyllie, S. ;
Singh, N. ;
Sundar, S. ;
Fairlamb, A. H. ;
Chatterjee, M. .
PARASITOLOGY, 2007, 134 :1679-1687
[10]   Characterization of natural antimony resistance in Leishmania donovani isolates [J].
Mittal, Mukul K. ;
Rai, Smita ;
Ravinder, Ashutosh ;
Gupta, Suman ;
Sundar, Shyam ;
Goyal, Neena .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2007, 76 (04) :681-688