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Differential gene expression analysis in antimony-unresponsive Indian kala azar (visceral leishmaniasis) clinical isolates by DNA microarray

  • N. SINGH (a1), R. ALMEIDA (a2), H. KOTHARI (a1), P. KUMAR (a1), G. MANDAL (a3), M. CHATTERJEE (a3), S. VENKATACHALAM (a4), M. K. GOVIND (a4), S. K. MANDAL (a1) and S. SUNDAR (a5)
  • DOI:
  • Published online: 01 February 2007

In this study, cDNA microarray analysis of a closely related species, Leishmania major, was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of Leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. Clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. Many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (SAG)-treated patients. Interestingly, genes on the array, showing changes in expression of over 2-fold revealed the identity of ABC transporters, which are known determinants of drug resistance in laboratory mutants. The functionality of the transporters was validated by flow cytometry which, being biologically informative, provides direct clues to gene function. The results suggest that isolate 39 could have developed resistance by an increased multidrug resistance protein (MRP)-like pump. This study provides preliminary clues to the role of a thiol-dependent efflux system in antimonial resistant clinical isolates of Leishmania donovani.

Corresponding author
*Corresponding author: Central Drug Research Institute, Lucknow, India. E-mail:
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

N. S. Akopyants , R. S. Matlib , E. N. Bukanova , M. R. Smeds , B. H. Brownstein , G. D. Stormo and S. M. Beverly (2004). Expression profiling using random genomic DNA microarrays identifies deferentially expressed genes associated with three major developmental stages of the protozoan parasite Leishmania major. Molecular and Biochemical Parasitology 136, 7186.

J. Alexander and D. G. Russell (1992). The interaction of Leishmania species with macrophages. Advances in Parasitology 31, 175254.

M. H. Cheok , W. Yang , C. H. Pui , J. R. Downing , C. Cheng , C. W. Naeve , M. V. Relling and W. E. Evens (2003). Treatment specific changes in gene expression discriminate in vivo drug response in human leukemia cells. Nature Genetics 34, 8590.

M. J. Chiquero , J. M. Perez-Victoria , F. O'valle , J. M. Gonzalez-Ros , R. G. del Moral , J. A. Ferragut , S. Castanys and F. Gamarro (1998). Altered drug membrane permeability in a multidrug-resistant Leishmania tropica line. Biochemical Pharmacology 55, 131139.

P. Chomezynski and N. Sacchi (1987). Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162, 156159.

W. S. Cleveland (1979). Robust locally weighted regression and smoothing scatterplots. Journal of the American Statistical Association 74, 829836.

S. L. Croft and G. H. Coombs (2003). Leishmaniasis- current chemotherapy and recent advances in the search for novel drugs. Trends in Parasitology 19, 502508.

S. Dey , B. Papadopoulou , A. Haimeur , G. Roy , K. Grondin , D. Dou , B. P. Rosen and M. Ouellette (1994). High level of arsenite resistance in Leishmania tarentolae is mediated by an active extrusion system. Molecular and Biochemical Parasitology 67, 4957.

S. Diehl , F. Diehl , N. M. El-Sayed , C. Clayton and J. D. Hoheisel (2002). Analysis of stage specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA- microarray. Molecular and Biochemical Parasitology 123, 115123.

A. Dube , N. Singh , S. Sundar and N. Singh (2005). Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persists in in vitro and in vivo experimental models. Parasitology Research 96, 216223.

K. El Fadili , N. Messier , P. Leprohon , G. Roy , C. Guimond , N. Trudel , N. G. Sarvia , B. Papadopoulou , D. Legare and M. Ouellette (2005). Role of the ABC transporter MRPA (PGPA) in antimony resistance in Leishmania infantum axenic and intracellular amastigotes. Antimicrobial Agents and Chemotherapy 49, 19881993.

M. Essodaigui , H. J. Broxterman and A. Garnier-Suillerot (1998). Kinetic analysis of calcein and calcein-acetoxymethylester efflux mediated by the multidrug resistance protein and P-glycoprotein. Biochemistry 37, 22432250.

B. Gourbal , N. Sonuc , H. Bhattacharjee , D. Legare , S. Sundar , M. Ouellette , B. P. Rosen and R. Mukhopadhyay (2004). Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. Journal of Biological Chemistry 279, 3101031017.

K. Grondin , A. Haimeur , R. Mukhopadhayay , B. P. Rosen and M. Ouellette (1997). Co-amplification of the gamma – glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite – resistant Leishmania tarentole. EMBO Journal 16, 30573065.

C. Guimond , N. Trudel , C. Brochu , N. Marquis , A. El Fadili , R. Peytavi , G. Briand , D. Richard , N. Messier , B. Papadopoulou , J. Corbeil , M. G. Bergeron , D. Legare and M. Ouellette (2003). Modulation of gene expression in Leishmania drug resistant mutants as determined by targeted DNA microarrays. Nucleic Acids Research 31, 58865896.

A. Haimeur , C. Brochu , P. Genest , B. Papadopoulou and M. Ouellette (2000). Amplification of the ABC transporter gene PGPA and increased trypanothione levels in potassium antimonyl tartrate Sb(III) resistant Leishmania tarentole. Molecular and Biochemical Parasitology 108, 131135.

Y. Hochberg (2002). A sharper Bonferroni procedure for multiple test of significance. Biometrika 75, 800802.

M. K. Kerr and G. A. Churchill (2001). Bootstrapping cluster analysis: assessing the reliability of conclusions from microarray experiments. Proceedings of the National Academy of Sciences, USA 98, 89618965.

M. A. Newton , C. M. Kendziroski , C. S. Richmond , F. R. Blattner and K. W. Tsui (2001). On differential variability of expression ratios: improving statistical inference about gene expression changes from microarray data. Journal of Computational Biology 8, 3752.

F. J. Perez-Victoria , S. Castanys and F. Gamarro (2003). Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug. Antimicrobial Agents and Chemotherapy 47, 23972403.

J. Quackenbush (2002). Microarray data normalization and transformation Nature Genetics 32 (Suppl.), 496501.

P. K. Rathod , K. Ganesan , R. E. Hayward , Z. Bozdech and J. L. Derisi (2002). DNA microarrays for malaria. Trends in Parasitology 18, 3945.

K. Rutherford , J. Parkhill , J. Crook , T. Horsnell , P. Rice , M. A. Rajandream and B. Barrel (2000). Artemis: sequence visualization and annotation. Bioinformatics 16, 944945.

S. Sundar (2001). Drug resistances in Indian visceral leishmaniasis. Tropical Medicine and International Health 6, 849854.

P. K. Tan , T. J. Downey , E. L. Spitznagel Jr., P. Eu , D. Fu , D. S. Dimitroy , R. A. Lempicki , B. M. Raaka and M. C. Cam (2003). Evaluation of gene expression measurements from commercial microarray platforms. Nucleic Acids Research 31, 56765684.

M. Wilson , J. Derisi , H. H. Kristensen , P. Imboden , S. Rane , P. O. Brown and G. K. Schoolnik (1999). Exploring drug induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proceedings of the National Academy of Sciences, USA 96, 1283312838.

Y. H. Yang , S. Dudoit , P. Luu , D. M. Lin , V. Peng , J. Ngai and T. P. Speed (2002). Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Research 30, e15.

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