Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII

被引：48

作者：

Choudhury, Kohelia ^{[1
]}

Zander, Dorothea ^{[1
]}

Kube, Michael ^{[2
]}

Reinhardt, Richard ^{[2
]}

Clos, Joachim ^{[1
]}

机构：

[1] Bernhard Nocht Inst Trop Med, RG Leishmaniasis, D-20359 Hamburg, Germany

[2] Max Planck Inst Mol Genet, Berlin, Germany

来源：

INTERNATIONAL JOURNAL FOR PARASITOLOGY | 2008年 / 38卷 / 12期

关键词：

Leishmania infantum; Miltefosine; Antimony; Functional cloning; Drug resistance; Cosmid;

D O I：

10.1016/j.ijpara.2008.03.005

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 treatment is a growing problem in efforts to control Old World leishmaniasis. Parasites resistant to new therapeutics such as miltefosine have not been reported from the field yet but based on experimental evidence, may appear soon. Therefore, we attempted to identify genetic markers that may correlate with miltefosine resistance. Using a functional cloning approach, we have isolated a gene from Leishmania infantum that, upon over-expression, confers protection not only against miltefosine, but also against Sb-III, the active principle of anti-leishmanial antimonials. The gene encodes a very large putative polypeptide of 299 kDa that shows no similarities to known proteins or functional motifs. Database mining and karyotyping experiments suggest that in L. infantum this gene is part of a 44-kbp duplicated region that is found on two separate chromosomes, CHR08 and CHR29. (C) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：1411 / 1423

页数：13

共 48 条

[1] Leishmania and human immunodeficiency virus coinfection: The first 10 years [J].

Alvar, J ;

Canavate, C ;

GutierrezSolar, B ;

Jimenez, M ;

Laguna, F ;

LopezVelez, R ;

Molina, R ;

Moreno, J .

CLINICAL MICROBIOLOGY REVIEWS, 1997, 10 (02) :298-+

[2] Oligoproline effects on polyglutamine conformation and aggregation [J].

Bhattacharyya, A ;

Thakur, AK ;

Chellgren, VM ;

Thiagarajan, G ;

Williams, AD ;

Chellgren, BW ;

Creamer, TP ;

Wetzel, R .

JOURNAL OF MOLECULAR BIOLOGY, 2006, 355 (03) :524-535

[3] HIGH CONSTITUTIVE LEVELS OF HEAT-SHOCK PROTEINS IN HUMAN-PATHOGENIC PARASITES OF THE GENUS LEISHMANIA [J].

BRANDAU, S ;

DRESEL, A ;

CLOS, J .

BIOCHEMICAL JOURNAL, 1995, 310 :225-232

[4] A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids [J].

Castanys-Munoz, Esther ;

Alder-Baerens, Nele ;

Pomorski, Thomas ;

Gamarro, Francisco ;

Castanys, Santiago .

MOLECULAR MICROBIOLOGY, 2007, 64 (05) :1141-1153

[5] Functional cloning as a means to-identify Leishmania genes involved in drug resistance [J].

Clos, J ;

Choudhury, K .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2006, 6 (02) :123-129

[6]

Croft SL, 2006, INDIAN J MED RES, V123, P399

[7] Leishmania/HIV co-infections:: epidemiology in Europe [J].

Desjeux, P ;

Alvar, J .

ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY, 2003, 97 :3-15

[8] Stage-specific activity of pentavalent antimony against Leishmania donovani axenic amastigotes [J].

Ephros, M ;

Bitnun, A ;

Shaked, P ;

Waldman, E ;

Zilberstein, D .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (02) :278-282

[9] Base-calling of automated sequencer traces using phred.: II.: Error probabilities [J].

Ewing, B ;

Green, P .

GENOME RESEARCH, 1998, 8 (03) :186-194

[10] Base-calling of automated sequencer traces using phred.: I.: Accuracy assessment [J].

Ewing, B ;

Hillier, L ;

Wendl, MC ;

Green, P .

GENOME RESEARCH, 1998, 8 (03) :175-185

← 1 2 3 4 5 →