1887

Abstract

Leishmaniasis causes significant morbidity and mortality worldwide. The disease is endemic in developing countries of tropical regions, and in recent years economic globalization and increased travel have extended its reach to people in developed countries. In the absence of effective vaccines and vector-control measures, the main line of defence against the disease is chemotherapy. Organic pentavalent antimonials [Sb(V)] have been the first-line drugs for the treatment of leishmaniasis for the last six decades, and clinical resistance to these drugs has emerged as a primary obstacle to successful treatment and control. A multiplicity of resistance mechanisms have been described in resistant mutants developed by stepwise increases of the concentration of either antimony [Sb(III)] or the related metal arsenic [As(III)], the most prevalent mechanism being upregulated Sb(III) detoxification and sequestration. With the availability of resistant field isolates, it has now become possible to elucidate mechanisms of clinical resistance. The present review describes the mechanisms of antimony resistance in and highlights the links between previous hypotheses and current developments in field studies. Unravelling the molecular mechanisms of clinical resistance could allow the prevention and circumvention of resistance, as well as rational drug design for the treatment of drug-resistant .

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2007-02-01
2024-12-05
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References

  1. Adhuna A., Saltora P., Bhatnagar R. 2000; Nitric oxide induced expression of stress proteins in virulent and avirulent promastigotes of Leishmania donovani . Immunol Lett 71:171–176 [CrossRef]
    [Google Scholar]
  2. Arana F. E., Perez-Victoria J. M., Repetto Y., Morello A., Castanys S., Gamarro F. 1998; Involvement of thiol metabolism in resistance to glucantime in Leishmania tropica . Biochem Pharmacol 56:1201–1208 [CrossRef]
    [Google Scholar]
  3. Ariyanayagam M. R., Fairlamb A. H. 2001; Ovothiol and trypanothione as antioxidants in trypanosomatids. Mol Biochem Parasitol 115:189–198 [CrossRef]
    [Google Scholar]
  4. Ashford R., Desjeux P., deRaadt P. 1992; Estimation of population at risk of infection and number of cases of Leishmaniasis. Parasitol Today 8:104–105 [CrossRef]
    [Google Scholar]
  5. Ashutosh Gupta S., Ramesh Sundar S., Goyal N. 2005; Use of Leishmania donovani field isolates expressing the luciferase reporter gene in in vitro drug screening. Antimicrob Agents Chemother 49:3776–3783 [CrossRef]
    [Google Scholar]
  6. Berman J. D., Waddell D., Hanson B. D. 1985; Biochemical mechanisms of the antileishmanial activity of sodium stibogluconate. Antimicrob Agents Chemother 27:916–920 [CrossRef]
    [Google Scholar]
  7. Berman J. D., Gallalee J. V., Best J. M. 1987a; Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid beta-oxidation in Leishmania mexicana amastigotes. Biochem Pharmacol 36:197–201 [CrossRef]
    [Google Scholar]
  8. Berman J. D., Gallalee J. V., Hansen B. D. 1987b; Leishmania mexicana : uptake of sodium stibogluconate (Pentostam) and pentamidine by parasite and macrophages. Exp Parasitol 64:127–131 [CrossRef]
    [Google Scholar]
  9. Brandonisio D., Spinelli R. 2002; Immune response to parasitic infections – an introduction. Curr Drug Target Immun Endocr Metabol Disorder 2:193–199 [CrossRef]
    [Google Scholar]
  10. Brochu C., Wang J., Roy G., Messier N., Wang X. Y., Saravia N. G., Ouellette M. 2003; Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. Antimicrob Agents Chemother 47:3073–3079 [CrossRef]
    [Google Scholar]
  11. Brochu C., Haimeur A., Ouellette M. 2004; The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite Leishmania . Cell Stress Chaperones 9:294–303 [CrossRef]
    [Google Scholar]
  12. Brost P., Elferink R. O. 2002; Mammalian ABC transporters in health and disease. Annu Rev Biochem 71:537–592 [CrossRef]
    [Google Scholar]
  13. Burguera J. L., Burguera M., Petit de Pena Y., Lugo A., Anez N. 1993; Selective determination of antimony (III) and antimony (IV) in serum and urine and of total antimony in skin biopsies of patients with entaneous Leishmaniasis treated with meglumine antimoniate. J Trace Elem Med Biol 10:66–70
    [Google Scholar]
  14. Callahan H. L., Beverley S. M. 1991; Heavy metal resistance: a new role for P-glycoproteins in Leishmania . J Biol Chem 266:18427–18430
    [Google Scholar]
  15. Callahan H. L., Roberts W. L., Rainey P. M., Beverley S. M. 1994; The PGPA gene of Leishmania major mediates antimony (SbIII) resistance by decreasing influx and not by increasing efflux. Mol Biochem Parasitol 68:145–149 [CrossRef]
    [Google Scholar]
  16. Callahan H. L., Portal A. C., Devereaux R., Grogl M. 1997; An axenic amastigote system for drug screening. Antimicrob Agents Chemother 41:818–822
    [Google Scholar]
  17. Carrio J., de Colmenares M., Riera C., Gallego M., Arboix M., Portus M. 2000; Leishmania infantum : stage-specific activity of pentavalent antimony related with the assay conditions. Exp Parasitol 95:209–214 [CrossRef]
    [Google Scholar]
  18. Carter K. C., Mullen A. B., Sundar S., Kenney R. T. 2001; Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of Leishmania donovani . Antimicrob Agents Chemother 45:3555–3559 [CrossRef]
    [Google Scholar]
  19. Carter K. C., Sundar S., Spickett C., Pereira O. C., Mullen A. B. 2003; The in vivo susceptibility of Leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis. Antimicrob Agents Chemother 47:1529–1535 [CrossRef]
    [Google Scholar]
  20. Carter K. C., Hutchison S., Boitelle A., Murray H. W., Sundar S., Mullen A. B. 2005; Sodium stibogluconate resistance in Leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy. Parasitology 131:747–757 [CrossRef]
    [Google Scholar]
  21. Carter K. C., Hutchison S., Henriquez F. L., Legare D., Ouellette M., Roberts C. W., Mullen A. B. 2006; Resistance of Leishmania donovani to sodium stibogluconate is related to the expression of host and parasite (gamma)-glutamylcysteine synthetase. Antimicrob Agents Chemother 50:88–95 [CrossRef]
    [Google Scholar]
  22. Centers for Disease Control 2004; Updates: cutaneous leishmaniasis in U.S. military personnel – Southwest/Central Asia; 2002–2004. Morb Mortal Wkly Rep 53:264–265
    [Google Scholar]
  23. Chan M. M., Triemer R. E., Fong D. 1991; Effect of the anti-microtubule drug oryzalin on growth and differentiation of the parasitic protozoan Leishmania mexicana . Differentiation 46:15–21 [CrossRef]
    [Google Scholar]
  24. Coelho A. C., Beverley S. M., Cotrim P. C. 2003; Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major . Mol Biochem Parasitol 130:83–90 [CrossRef]
    [Google Scholar]
  25. Croft S. L., Neame K. D., Homewood C. A. 1981; Accumulation of [125Sb] sodium stibogluconate by Leishmania mexicana amazonensis and Leishmania donovani in vitro . Comp Biochem Physiol C 68C:95–98
    [Google Scholar]
  26. Croft S. L., Sundar S., Fairlamb A. H. 2006; Drug resistance in Leishmaniasis. Clin Microbiol Rev 19:111–126 [CrossRef]
    [Google Scholar]
  27. Cunningham M. L., Fairlamb A. H. 1995; Trypanothione reductase from Leishmania donovani . Purification, characterization and inhibition by trivalent antimonials. Eur J Biochem 230:460–468 [CrossRef]
    [Google Scholar]
  28. Cunningham M. L., Zvelebil M. J., Fairlamb A. H. 1994; Mechanism of inhibition of trypanothione reductase and glutathione reductase by trivalent organic arsenicals. Eur J Biochem 221:285–295 [CrossRef]
    [Google Scholar]
  29. Decuypere S., Rijal S., Yardley V., De Doncker S., Laurent T., Khanal B., Chappuis F., Dujardin J. C. 2005; Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal. Antimicrob Agents Chemother 49:4616–4621 [CrossRef]
    [Google Scholar]
  30. Denton H., McGregor J. C., Coombs G. H. 2004; Reduction of antileishmanial pentavalent antimonial drugs by a parasite-specific thiol dependent reductase TDR1. Biochem J 381:405–412 [CrossRef]
    [Google Scholar]
  31. Desjeux P. 2000 Leishmania and HIV Co-infection in Southwestern Europe, 1990–1998, Retrospective Analysis of 965 Cases Geneva: World Health Organization;
    [Google Scholar]
  32. Desjeux P. 2001; The increase in risk factors of leishmaniasis worldwide. Trans R Soc Trop Med Hyg 95:239–243 [CrossRef]
    [Google Scholar]
  33. Dey S., Papadopoulou B., Haimeur A., Roy G., Grondin K., Dou D., Rosen B. P., Ouellette M. 1994; High level arsenite resistance in Leishmania tarentolae is mediated by an active extrusion system. Mol Biochem Parasitol 67:49–57 [CrossRef]
    [Google Scholar]
  34. Dey S., Ouellette M., Lightbody J., Papadopoulou B., Rosen B. P. 1996; An ATP-dependent As(III)-glutathione transport system in membrane vesicles of Leishmania tarentolae . Proc Natl Acad Sci U S A 93:2192–2197 [CrossRef]
    [Google Scholar]
  35. El Fadili K., Messier N., Leprohon P., Roy G., Guimond C., Trudel N., Saravia N. G., Papadopoulou B., Legare D., Ouellette M. 2005; Role of the ABC transporter MRPA (PGPA) in antimony resistance in Leishmania infantum axenic and intracellular amastigotes. Antimicrob Agents Chemother 49:1988–1993 [CrossRef]
    [Google Scholar]
  36. Ellenberger T. E., Beverley S. M. 1989; Multiple drug resistance and conservative amplification of the H region in Leishmania major . J Biol Chem 264:15094–15103
    [Google Scholar]
  37. Ephros M., Waldman E., Zilberstein D. 1997; Pentostam induces resistance to antimony and the preservative chlorocresol in Leishmania donovani promastigotes and axenically grown amastigotes. Antimicrob Agents Chemother 41:1064–1068
    [Google Scholar]
  38. Ephros M., Bitnun A., Shaked P., Waldman E., Zilberstein D. 1999; Stage-specific activity of pentavalent antimony against Leishmania donovani axenic amastigotes. Antimicrob Agents Chemother 43:278–282
    [Google Scholar]
  39. Fairlamb A. H., Cerami A. 1992; Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 46:695–729 [CrossRef]
    [Google Scholar]
  40. Faraut-Gambbarelli F., Pioroux R., Deniau M., Giusiano B., Marty G., Faugere B., Dumon H. 1997; In vitro resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis. Antimicrob Agents Chemother 41:827–830
    [Google Scholar]
  41. Ferreira Cdos S., Martins P. S., Demicheli C., Brochu C., Ouellette M., Frezard F. 2003; Thiol-induced reduction of antimony (V) into antimony (III): a comparative study with trypanothione, cysteinyl-glycine, cysteine and glutathione. Biometals 16:441–446 [CrossRef]
    [Google Scholar]
  42. Ferreira-Pinto K. C., Miranda-Vilela A. L., Anacleto C., Fernandes A. P., Abdo M. C., Petrillo-Peixoto M. L., Moreira E. S. 1996; Leishmania ( V .) guyanensis : isolation and characterization of glucantime-resistant cell lines. Can J Microbiol 42:944–949 [CrossRef]
    [Google Scholar]
  43. Frezard F., Demicheli C., Ferreira C. S., Costa M. A. 2001; Glutathione-induced conversion of pentavalent antimony to trivalent antimony in meglumine antimoniate. Antimicrob Agents Chemother 45:913–916 [CrossRef]
    [Google Scholar]
  44. Glaser T. A., Baatz J. E., Kreishman G. P., Mukkada A. J. 1988; pH homeostasis in Leishmania donovani amastigotes and promastigotes. Proc Natl Acad Sci U S A 85:7602–7606 [CrossRef]
    [Google Scholar]
  45. Gourbal B., Sonuc N., Bhattacharjee H., Legare D., Sundar S., Ouellette M., Rosen B. P., Mukhopadhyay R. 2004; Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J Biol Chem 279:31010–31017 [CrossRef]
    [Google Scholar]
  46. Goyard S., Segawa H., Gordon J., Showalter M., Duncan R., Turco S. J., Beverley S. M. 2003; An in vitro system for developmental and genetic studies of Leishmania donovani phosphoglycans. Mol Biochem Parasitol 130:31–42 [CrossRef]
    [Google Scholar]
  47. Grondin K., Haimeur A., Mukhopadhyay R., Rosen B. P., Ouellette M. 1997; Co-amplification of the gamma-glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite-resistant Leishmania tarentolae . EMBO J 16:3057–3065 [CrossRef]
    [Google Scholar]
  48. Guerin P. J., Olliaro P., Sunder S., Boelaeri M., Croft S. L., Desjeux P., Wasunna M. K., Bryceson A. D. 2002; Visceral leishmaniasis: current status of control, diagnosis and treatment, and a proposed research and development agenda. Lancet Infect Dis 2:494–501 [CrossRef]
    [Google Scholar]
  49. Guimond C., Trudel N., Brochu C., Marquis N., El Fadili A., Peytavi R., Briand G., Richard D., Messier N. other authors 2003; Modulation of gene expression in Leishmania drug resistant mutants as determined by targeted DNA microarrays. Nucleic Acids Res 31:5886–5896 [CrossRef]
    [Google Scholar]
  50. Gundersen G. G., Cook T. A. 1999; Microtubules and signal transduction. Curr Opin Cell Biol 11:81–94 [CrossRef]
    [Google Scholar]
  51. Haimeur A., Brochu C., Genest P., Papadopoulou B., Ouellette M. 2000; Amplification of the ABC transporter gene PGPA and increased trypanothione levels in potassium antimonyl tartrate (SbIII) resistant Leishmania tarentolae . Mol Biochem Parasitol 108:131–135 [CrossRef]
    [Google Scholar]
  52. Haimeur A., Ouellette M. 1998; Gene amplification in Leishmania tarentolae selected for resistance to sodium stibogluconate. Antimicrob Agents Chemother 42:1689–1694
    [Google Scholar]
  53. Haimeur A., Guimond C., Pilote S., Mukhopadhyay R., Rosen B. P., Poulin R., Ouellette M. 1999; Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite-resistant Leishmania . Mol Microbiol 34:726–735 [CrossRef]
    [Google Scholar]
  54. Haimeur A., Conseil G., Deeley R. G., Cole S. P. 2004; Mutations of charged amino acids in or near the transmembrane helices of the second membrane spanning domain differentially affect the substrate specificity and transport activity of the multidrug resistance protein MRP1 (ABCC1). Mol Pharmacol 65:1375–1385 [CrossRef]
    [Google Scholar]
  55. Herwaldt B. L. 1999; Leishmaniasis. Lancet 354:1191–1199 [CrossRef]
    [Google Scholar]
  56. Holzmuller P., Sereno D., Cavaleyra M., Mangot I., Daulouede S., Vincendeau P., Lemesre J. L. 2002; Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes. Infect Immun 70:3727–3735 [CrossRef]
    [Google Scholar]
  57. Holzmuller P., Sereno D., Lemesre J. L. 2005; Lower nitric oxide susceptibility of trivalent antimony-resistant amastigotes of Leishmania infantum . Antimicrob Agents Chemother 49:4406–4409 [CrossRef]
    [Google Scholar]
  58. Jang J. H., Surh Y. J. 2004; Bcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kB activation. J Biol Chem 279:38779–38786 [CrossRef]
    [Google Scholar]
  59. Jayanarayan K. G., Dey C. S. 2002; Resistance to arsenite modulates expression of beta- and gamma-tubulin and sensitivity to Paclitaxel during differentiation of Leishmania donovani . Parasitol Res 88:754–759 [CrossRef]
    [Google Scholar]
  60. Jayanarayan K. G., Dey C. S. 2004; Altered expression, polymerisation and cellular distribution of alpha-/beta-tubulins and apoptosis-like cell death in arsenite resistant Leishmania donovani promastigotes. Int J Parasitol 34:915–925 [CrossRef]
    [Google Scholar]
  61. Klokouzas A., Shahi S., Hladky S. B., Barrand M. A., Van Veen H. W. 2003; ABC transporters and drug resistance in parasitic protozoa. Int J Antimicrob Agents 22:301–317 [CrossRef]
    [Google Scholar]
  62. Lawrence F., Robert-Gero M. 1985; Induction of heat shock and stress proteins in promastigotes of three Leishmania species. Proc Natl Acad Sci U S A 82:4414–4417 [CrossRef]
    [Google Scholar]
  63. Leandro C., Campino L. 2003; Leishmaniasis: efflux pumps and chemoresistance. Int J Antimicrob Agents 22:352–357 [CrossRef]
    [Google Scholar]
  64. Lecureur V., Lagadic-Gossmann D., Fardel O. 2002; Potassium antimonyl tartrate induces reactive oxygen species-related apoptosis in human myeloid leukemic HL60 cells. Int J Oncol 20:1071–1076
    [Google Scholar]
  65. Lee N., Bertholet S., Debrabant A., Muller J., Duncan R., Nakhasi H. L. 2002; Programmed cell death in the unicellular protozoan parasite Leishmania . Cell Death Differ 9:53–64 [CrossRef]
    [Google Scholar]
  66. Légaré D., Papadopoulou B., Roy G., Mukhopadhyay R., Haimeur A., Dey S., Grondin K., Brochu C., Rosen B. P., Ouellette M. 1997; Efflux systems and increased trypanothione levels in arsenite resistant Leishmania species. Exp Parasitol 87:275–282 [CrossRef]
    [Google Scholar]
  67. Légaré D., Richard D., Mukhopadhyay R., Stierhof Y. D., Rosen B. P., Haimeur A., Papadopoulou B., Ouellette M. 2001; The Leishmania ATP-binding casstte protein PGPA is an intracellular metal–thiol transporter ATPase. J Biol Chem 276:26301–26307 [CrossRef]
    [Google Scholar]
  68. Lira R., Sunder S., Makharia A., Kenney R., Gam A., Saraiva E., Sack D. 1999; Evidence that incidence of treatment failure in Indian kala-azar is due to the emergence of antimony resistant strains of Leishmania donovani . J Infect Dis 180:564–567 [CrossRef]
    [Google Scholar]
  69. Liu Z., Shen J., Carbrey J. M., Mukhopadhyay R., Agre P., Rosen B. P. 2002; Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc Natl Acad Sci U S A 99:6053–6058 [CrossRef]
    [Google Scholar]
  70. Lo J. F., Wang H. F., Tam M. F., Lee T. C. 1992; Glutathione S -transferase pi in an arsenic-resistant Chinese hamster ovary cell line. Biochem J 288:977–982
    [Google Scholar]
  71. Lugo de Yarbuh A., Anez N., Petit de Pena Y., Burguera J. L., Burguera M. 1994; Antimony determination in tissue and serum of hamsters infected with Leishmania garnhami and treated with meglumine antimoniate!. Ann Trop Med Parasitol 88: !N., Gourbal, B., Rosen, B. P., Mukhopadhyay, R. & Ouellette, M. (2005). Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania . Mol Microbiol 57 1690–1699 [CrossRef]
    [Google Scholar]
  72. Meister A., Anderson M. E. 1983; Glutathione. Annu Rev Biochem 52:711–760 [CrossRef]
    [Google Scholar]
  73. Miller M. A., McGowan S. E., Gantt K. R., Champion M., Novick S. L., Andersen K. A., Bacchi C. J., Yarlett N., Britigan B. E., Wilson M. E. 2000; Inducible resistance to oxidant stress in the protozoan Leishmania chagasi . J Biol Chem 275:33883–33889 [CrossRef]
    [Google Scholar]
  74. Mishra M., Biswas U. K., Jha D. N., Khan A. B. 1992; Amphotericin versus pentamidine in antimony-unresponsive kala-azar. Lancet 340:1256–1257
    [Google Scholar]
  75. Molyneux D., Killick-Kendrick R. 1987; Morphology, ultrastructure and lifecycles. In Leishmaniasis in Biology and Medicine vol. 1 pp  121–176 Edited by Peters W., Killick-Kendrick R. London: Academic Press; [CrossRef]
    [Google Scholar]
  76. Mukhopadhyay R., Rosen B. P. 1998; Saccharomyces cerevisiae ACR2 gene encodes an arsenate reductase. FEMS Microbiol Lett 168:127–136 [CrossRef]
    [Google Scholar]
  77. Mukhopadhyay R., Rosen B. P. 2001; The phosphatase C( X )5R motif is required for catalytic activity of the Saccharomyces cerevisiae Acr2p arsenate reductase. J Biol Chem 276:34738–34742 [CrossRef]
    [Google Scholar]
  78. Mukhopadhyay R., Rosen B. P. 2002; Arsenate reductases in prokaryotes and eukaryotes. Environ Health Perspect 110:745–748 [CrossRef]
    [Google Scholar]
  79. Mukhopadhyay R., Dey S., Xu N., Gage D., Lightbody J., Ouellette M., Rosen B. P. 1996; Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania . Proc Natl Acad Sci U S A 93:10383–10387 [CrossRef]
    [Google Scholar]
  80. Mukhopadhyay R., Shi J., Rosen B. P. 2000; Purification and characterization of Acr2p, the Saccharomyces cerevisiae arsenate reductase. J Biol Chem 275:21149–21157 [CrossRef]
    [Google Scholar]
  81. Murray H. W. 2001; Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob Agents Chemother 45:2185–2197
    [Google Scholar]
  82. Ouellette M., Hettema E., Wust D., Fase-Fowler F., Borst P. 1991; Direct and inverted DNA repeats associated with P-glycoprotein gene amplification in drug resistant Leishmania . EMBO J 10:1009–1016 [CrossRef]
    [Google Scholar]
  83. Ouellette M., Légaré D., Haimeur A., Grondin K., Roy G., Brochu C., Papadopoulou B. 1998; ABC transporters in Leishmania and their role in drug resistance. Drug Resist Updat 1:43–48
    [Google Scholar]
  84. Ouellette M., Legare D., Papadopoulou B. 2001; Multidrug resistance and ABC transporters in parasitic protozoa. J Mol Microbiol Biotechnol 3:201–206 [CrossRef]
    [Google Scholar]
  85. Ouellette M., Drummelsmith J., Papadopoulou B. 2004; Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Updat 7:257–266
    [Google Scholar]
  86. Papadopoulou B., Roy G., Dey S., Rosen B. P., Ouellette M. 1994; Contribution of the Leishmania P-glycoprotein-related gene ltpgpA to oxyanion resistance. J Biol Chem 269:11980–11986 [CrossRef]
    [Google Scholar]
  87. Pathak M. K., Yi T. 2001; Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines. J Immunol 167:3391–3397 [CrossRef]
    [Google Scholar]
  88. Perez-Victoria F. J., Castanys S., Gamarro F. 2003; Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug. Antimicrob Agents Chemother 47:2397–2403 [CrossRef]
    [Google Scholar]
  89. Prasad V., Dey C. S. 2000; Tubulin is hyperphosphorylated on serine and tyrosine residues in arsenite-resistant Leishmania donovani promastigotes. Parasitol Res 86:876–880 [CrossRef]
    [Google Scholar]
  90. Prasad V., Kumar S. S., Dey C. 2000; Resistance to arsenite modulates levels of α -tubulin and sensitivity to Paclitaxel in Leishmania donovani . Parasitol Res 86:838–842 [CrossRef]
    [Google Scholar]
  91. Ramirez P., Eastmond D. A., Laclette J. P., Ostrosky-Wegman P. 1997; Disruption of microtubule assembly and spindle formation as a mechanism for the induction of aneuploid cells by sodium arsenite and vanadium pentoxide. Mutat Res 386:291–298 [CrossRef]
    [Google Scholar]
  92. Roberts W. L., Rainey P. M. 1993; Antileishmanial activity of sodium stibogluconate fractions. Antimicrob Agents Chemother 37:1842–1846 [CrossRef]
    [Google Scholar]
  93. Roberts W. L., Berman J. D., Rainey P. M. 1995; In vitro antileishmanial properties of tri- and pentavalent antimonial preparations. Antimicrob Agents Chemother 39:1234–1239 [CrossRef]
    [Google Scholar]
  94. Rosen B. P. 2002; Transport and detoxification systems for transition metals, heavy metals and metalloids in eukaryotic and prokaryotic microbes. Comp Biochem Physiol A Mol Integr Physiol 133:689–693 [CrossRef]
    [Google Scholar]
  95. Rosenthal E., Marty P., Poizot-Martin I., Reynes J., Pratlong F., Lafeuillade A., Jaubert D., Boulat O., Dereure J. other authors 1995; Visceral leishmaniasis and HIV-1 co-infection in Southern France. Trans R Soc Trop Med Hyg 89:159–162 [CrossRef]
    [Google Scholar]
  96. Rosypal A. C., Troy G. C., Zajac A. M., Duncun R. B. Jr, Waki K., Chang K. P., Lindsay D. S. 2003; Emergence of zoonotic canine leishmaniasis in the United States: isolation and immunohistochemical detection of Leishmnia infantum from foxhounds from Virginia. J Eukaryot Microbiol 50:691–693
    [Google Scholar]
  97. Sanders O. I., Rensing C., Kuroda M., Mitra B., Rosen B. P. 1997; Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli . J Bacteriol 179:3365–3367
    [Google Scholar]
  98. Sereno D., Lemesre J. L. 1997; Axenically cultured amastigote forms as an in vitro model for investigation of antileishmanial agents. Antimicrob Agents Chemother 41:972–976
    [Google Scholar]
  99. Sereno D., Cavaleyra M., Zemzoumi K., Maquaire S., Ouaissi A., Lemesre J. L. 1998; Axenically grown amastigotes of Leishmania infantum used as an in vitro model to investigate the pentavalent antimony mode of action. Antimicrob Agents Chemother 42:3097–3102 [CrossRef]
    [Google Scholar]
  100. Sereno D., Holzmuller P., Mangot I., Cuny G., Ouaissi A., Lemesre J. L. 2001; Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrob Agents Chemother 45:2064–2069 [CrossRef]
    [Google Scholar]
  101. Shaked-Mishan P., Ulrich N., Ephros M., Zilberstein D. 2001; Novel intracellular SbV reducing activity correlates with antimony susceptibility in Leishmania donovani . J Biol Chem 276:3971–3976 [CrossRef]
    [Google Scholar]
  102. Sudhandiran G., Shaha C. 2003; Antimonial-induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J Biol Chem 278:25120–25132 [CrossRef]
    [Google Scholar]
  103. Sun H., Yan S. C., Cheng S. C. 2000; Interaction of antimony tartrate with the tripeptide glutathione implication for its mode of action. Eur J Biochem 267:5450–5457 [CrossRef]
    [Google Scholar]
  104. Sundar S. 2001; Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 6:849–854
    [Google Scholar]
  105. Sundar S., Murray H. W. 2005; Availability of miltefosine for the treatment of kala-azar in India. Bull World Health Organ 83:394–395 [CrossRef]
    [Google Scholar]
  106. Sundar S., Gupta L. B., Makharia M. K., Singh M. K., Voss A., Rosenkaimer F., Engel J., Murray H. W. 1999; Oral treatment of visceral leishmaniasis with miltefosine. Ann Trop Med Parasitol 93:589–597 [CrossRef]
    [Google Scholar]
  107. Sundar S., More D. K., Singh M. K., Singh V. P., Sharma S., Makharia A., Kumar P. C., Murray H. W. 2000; Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31:1104–1106 [CrossRef]
    [Google Scholar]
  108. Tamas M. J., Wysocki R. 2001; Mechanisms involved in metalloid transport and tolerance acquisition. Curr Genet 40:2–12 [CrossRef]
    [Google Scholar]
  109. Tsukaguchi H., Shayakul C., Berger U. V., Mackenzie B., Devidas S., Guggino W. B., Van Hoek A. N., Hediger M. A. 1998; Molecular characterization of a broad selectivity neutral solute channel. J Biol Chem 273:24737–24743
    [Google Scholar]
  110. Tsukaguchi H., Weremowicz S., Morton C. C., Hediger M. A. 1999; Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol 277:F685–F696 [CrossRef]
    [Google Scholar]
  111. Vicker T. J., Fairlamb A. H. 2004; Trypanothione S -transferase activity in a trypanosomatid ribosomal elongation factor 1B. J Biol Chem 279:27246–27256 [CrossRef]
    [Google Scholar]
  112. Webster P., Russell D. G. 1993; The flagellar pocket of trypanosomatids. Parasitol Today 9:201–206
    [Google Scholar]
  113. Weise F., Stierhof Y. D., Kuhn C., Wiese M., Overath P. 2000; Distribution of GPI-anchored proteins in the protozoan parasite Leishmania , based on an improved ultrastructural description using high-pressure frozen cells. J Cell Sci 113:4587–4603 [CrossRef]
    [Google Scholar]
  114. Wyllie S., Fairlamb A. H. 2006; Differential toxicity of antimonial compounds and their effects on glutathione homeostasis in a human leukaemia monocyte cell line. Biochem Pharmacol 71:257–267 [CrossRef]
    [Google Scholar]
  115. Wyllie S., Cunningham M. L., Fairlamb A. H. 2004; Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani . J Biol Chem 279:39925–39932 [CrossRef]
    [Google Scholar]
  116. Wysocki R., Chery C. C., Wawrzycka D., Van Hulle M., Cornelis R., Thevelein J. M., Tamas M. J. 2001; The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae . Mol Microbiol 40:1391–1401 [CrossRef]
    [Google Scholar]
  117. Yan J., Kline A. D., Mo H., Shapiro M. J., Zartler E. R. 2003; The effect of relaxation on the epitope mapping by saturation transfer difference NMR. J Magn Reson 163:270–276 [CrossRef]
    [Google Scholar]
  118. Yan S., Li F., Ding K., Sun H. 2003a; Reduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione. J Biol Inorg Chem 8:689–697
    [Google Scholar]
  119. Yan S., Wong I. L., Chow L. M., Sun H. 2003b; Rapid reduction of pentavalent antimony by trypanothione: potential relevance to antimonial activation. Chem Commun ( Camb ) 2:266–267 [CrossRef]
    [Google Scholar]
  120. Zhou Y., Messier N., Ouellette M., Rosen B. P., Mukhopadhyay R. 2004; Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam. J Biol Chem 279:37445–37451
    [Google Scholar]
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