Molecular characterization of the MRPA transporter and antimony uptake in four New World Leishmania spp. susceptible and resistant to antimony

International Journal for Parasitology: Drugs and Drug Resistance

Volumn 3, Issue , 2013, Pages 143-153

  Moreira, Douglas S ^a   Monte Neto, Rubens L ^b,c   Andrade, Juvana M ^a   Santi, Ana Maria M ^a   Reis, Priscila G ^b   Frézard, Frédéric ^b   Murta, Silvane M F ^a  

^a INSTITUTO OSWALDO CRUZ   (Brazil)

^b FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

^c LAVAL UNIVERSITY   (Canada)

Author keywords

Drug resistance; Leishmania spp.; MRPA transporter; Potassium antimonyl tartrate

Indexed keywords

ANTIMONY; AQUAGLYCEROPORIN; MULTIDRUG RESISTANCE PROTEIN;

ARTICLE; ATOMIC ABSORPTION SPECTROMETRY; LEISHMANIA; LEISHMANIA BRAZILIENSIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR DOWN REGULATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

EID: 84884177036     PISSN: 22113207     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ijpddr.2013.08.001     Document Type: Article

References (67)

1. Adaui V., Schnorbusch K., Zimic M., Gutiérrez A., Decuypere S., Vanaerschot M., Doncker D.E., Maes S., Llanos-Cuentas I., Chappuis A., Arévalo F., Dujardin J. Comparison of gene expression patterns among Leishmania braziliensis clinical isolates showing a different in vitro susceptibility to pentavalent antimony. Parasitology 2011, 138:183-193.
2. Alvar J., Vélez I.D., Bern C., Herrero M., Desjeux P., Cano J., Jannin J., den Boer M., W.H.O.Leishmaniasis Control Team Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012, 7(5):e35671. 10.1371/journal.pone.0035671.
3. Anacleto C., Abdo M.C., Ferreira A.V., Murta S.M., Romanha A.J., Fernandes A.P., Moreira E.S. Structural and functional analysis of an amplification containing a PGPA gene in a glucantime-resistant Leishmania (Viannia) guyanensis cell line. Parasitol. Res. 2003, 90:110-118.
4. Ashford R.W., Seaman J., Schorscher J., Pratlong F. Epidemic visceral leishmaniasis in southern Sudan: identity and systematic position of the parasites from patients and vectors. Trans. R. Soc. Trop. Med. Hyg. 1992, 86:379-380.
5. Ashutosh, Sundar S., Goyal N. Molecular mechanisms of antimony resistance in Leishmania. J. Med. Microbiol. 2007, 56:143-153.
6. Basu J.M., Mookerjee A., Sen P., Bhaumik S., Banerjee S., Naskar K., Choudhuri S.K., Saha B., Raha S., Roy S. Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages. Antimicrob. Agents Chemother. 2006, 50:1788-1797.
7. Beverley S.M. Characterization of the 'unusual' mobility of large circular DNAs in pulse-field gradient electrophoresis. Nucleic Acids Res. 1988, 16:925-939.
8. Beverley S.M. Gene amplification in Leishmania. Annu. Rev. Microbiol. 1991, 45:417-444.
9. Borgnia M., Nielsen S., Engel A., Agre P. Cellular and molecular biology of aquaporin water channels. Annu. Rev. Biochem. 1999, 68:425-458.
10. Borst P., Evers R., Kool M., Winholds J. A family of drug transporters: the multidrug resistance-associated proteins. J. Natl. Cancer Inst. 2000, 92:1295-1302.
11. Brochu C., Wang J., Roy G., Messier N., Wang X.Y., Saravia N.G., Ouellette M. Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. Antimicrob. Agents Chemother. 2003, 47:3073-3079.
12. Cornwell M.M., Pastan I., Gottesman M.M. Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein. J. Biol. Chem. 1987, 262:2166-2170.
13. Croft S.L., Sundar S., Fairlamb A.H. Drug resistance in Leishmaniasis. Clin. Microbiol. Rev. 2006, 19:111-126.
14. Dassa E., Bouige P. The ABC of ABCs: a phylogenetic and functional classification of ABC systems in living organisms. Res. Microbiol. 2001, 152:211-229.
15. Decuypere S., Rijal S., Yardley V., De Doncker S., Laurent T., Khanal B., Chappuis F., Dujardin J.C. Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal. Antimicrob. Agents Chemother. 2005, 49:4616-4621.
16. Decuypere S., Vanaerschot M., Brunker K., Imamura H., Muller S., Khanal B., Rijal S., Dujardin J.C., Coombs G.H. Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background. PLoS Negl. Trop. Dis. 2012, 6:e1514.
17. Dias F.C., Ruiz J.C., Lopes W.C., Squina F.M., Renzi A., Cruz A.K., Tosi L.R. Organization of H locus conserved repeats in Leishmania (Viannia) braziliensis correlates with lack of gene amplification and drug resistance. Parasitol. Res. 2007, 101:667-676.
18. Downing T., Imamura H., Decuypere S., Clark T.G., Coombs G.H., Cotton J.A., Hilley J.D., de Doncker S., Maes I., Mottram J.C., Quail M.A., Rijal S., Sanders M., Schönian G., Stark O., Sundar S., Vanaerschot M., Hertz-Fowler C., Dujardin J.C., Berriman M. Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Res. 2011, 21:2143-2156.
19. El Fadili K., Messier N., Leprohon P., Roy G., Guimond C., Trudel N., Saravia N.G., Papadopoulou B., Légaré D., Ouellette M. Role of the ABC transporter MRPA (PGPA) in antimony resistance in Leishmania infantum axenic and intracellular amastigotes. Antimicrob. Agents Chemother. 2005, 49:1988-1993.
20. Frézard F., Demicheli C., Ribeiro R.R. Pentavalent antimonials: new perspectives for old drugs. Molecules 2009, 14:2317-2336.
21. Gamarro F., Chiquero M.J., Amador M.V., Légaré D., Ouellette M., Castanys S. P-glycoprotein overexpression in methotrexate-resistant Leishmania tropica. Biochem. Pharmacol. 1994, 47:1939-1947.
22. Gourbal B., Sonuc N., Bhattacharjee H., Légaré D., Sundar S., Ouellette M., Rosen B.P., Mukhopadhyay R. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 2004, 279:31010-31017.
23. Griffith O.W., Meister A. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J. Biol. Chem. 1979, 254:7558-7560.
24. Grogl M., Martin R.K., Oduola A.M., Milhous W.K., Kyle D.E. Characteristics of multidrug resistance in Plasmodium and Leishmania: detection of P-glycoprotein-like components. Am. J. Trop. Med. Hyg. 1991, 45:98-111.
25. Grondin K., Haimeur A., Mukhopadhyay R., Rosen B.P., Ouellette M. Co-amplification of the gamma-glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite-resistant Leishmania tarentolae. EMBO J. 1997, 16:3057-3065.
26. Grondin K., Kundig C., Roy G., Ouellette M. Linear amplicons as precursors of amplified circles in methotrexate-resistant Leishmania tarentolae. Nucleic Acids Res. 1998, 26:3372-3378.
27. Henriksson J., Pettersson U., Solari A. Trypanosoma cruzi: correlation between karyotype variability and isoenzyme classification. Exp. Parasitol. 1993, 77:334-348.
28. Herwaldt B.L. Leishmaniasis. Lancet 1999, 354:1191-1199.
29. Higgins C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 1992, 8:67-113.
30. Jeddi F., Piarroux R., Mary C. Antimony resistance in Leishmania, focusing on experimental research. J. Trop. Med. 2011, 695382. 10.1155/2011/695382.
31. Kuhls K., Keilonat L., Ochsenreither S., Schaar M., Schweynoch C., Presber W., Schönian G. Multilocus microsatellite typing (MLMT) reveals genetically isolated populations between and within the main endemic regions of visceral leishmaniasis. Microbes Infect. 2007, 9:334-343.
32. Lee N., Bertholet S., Debrabant A., Muller J., Duncan R., Nakhasi H.L. Programmed cell death in the unicellular protozoan parasite Leishmania. Cell Death Differ. 2002, 9:53-64.
33. Légaré D., Richard D., Mukhopadhyay R., Stierhof Y.D., Rosen B.P., Haimeur A., Papadopoulou B., Ouellette M. The Leishmania ABC protein PGPA is an intracellular metal-thiol transporter ATPase. J. Biol. Chem. 2001, 276:26301-26307.
34. Leprohon P., Légaré D., Raymond F., Madore F., Hardiman G., Corbeil J., Ouellette M. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Res. 2009, 37:1387-1399.
35. Liarte D.B., Murta S.M.F. Selection and phenotype characterization of potassium antimony tartrate-resistant populations of four New World Leishmania species. Parasitol. Res. 2010, 107:205-212.
36. Maharjan M., Singh S., Chatterjee M., Madhubala R. Role of aquaglyceroporin (AQP1) gene and drug uptake in antimony-resistant clinical isolates of Leishmania donovani. Am. J. Trop. Med. Hyg. 2008, 79:69-75.
37. Marquis N., Gourbal B., Rosen B.P., Mukhopadhyay R., Ouellette M. Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. Mol. Microbiol. 2005, 57:1690-1699.
38. Marzochi M.C., Marzochi K.B. Tegumentary and visceral leishmaniases in Brazil: emerging anthropozoonosis and possibilities for their control. Cad Saude Publica 1994, 2:359-375.
39. Monte Neto R.L., Coelho A.C., Raymond F., Légaré D., Corbeil J., Melo M.N., Frézard F., Ouellette M. Gene expression profiling and molecular characterization of antimony resistance in Leishmania amazonensis. PLoS Negl. Trop. Dis. 2011, 5:e1167. 10.1371/journal.pntd. 0001167.
40. Moreira E.S., Anacleto C., Petrillo-Peixoto M.L. Effect of glucantime on field and patient isolates of New World Leishmania: use of growth parameters of promastigotes to assess antimony susceptibility. Parasitol. Res. 1998, 84:720-726.
41. Moreira W., Leprohon P., Ouellette M. Tolerance to drug-induced cell death favours the acquisition of multidrug resistance in Leishmania. Cell Death Dis. 2011, 2:e201.
42. Mukherjee A., Padmanabhan P.K., Singh S., Roy G., Girard I., Chatterjee M., Ouellette M., Madhubala R. Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. J. Antimicrob. Chemother. 2007, 59:204-211.
43. Mukherjee A., Boisvert S., Monte-Neto R.L., Coelho A.C., Raymond F., Mukhopadhyay R., Corbeil J., Ouellette M. Telomeric gene deletion and intrachromosomal amplification in antimony-resistant Leishmania. Mol. Microbiol. 2013, 88:189-202.
44. Murray H.W. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob. Agents Chemother. 2001, 45:2185-2197.
45. Murray H.W., Nathan C.F. In vivo killing of intracellular visceral Leishmania donovani by a macrophage-targeted hydrogen peroxide-generating system. J. Infect. Dis. 1988, 158:1372-1375.
46. Murray H.W., Berman J.D., Davies C.R., Saravia N.G. Advances in leishmaniasis. Lancet 2005, 366:1561-1577.
47. Murta S.M., dos Santos W.G., Anacleto C., Nirdé P., Moreira E.S., Romanha A.J. Drug resistance in Trypanosoma cruzi is not associated with amplification or overexpression of P-glycoprotein (PGP) genes. Mol. Biochem. Parasitol. 2001, 117:223-228.
48. Ouellette M., Borst P. Drug resistance and P-glycorpotein in the protozoan parasite Leishmania. Res. Microbiol. 1991, 142:737-746.
49. Ouellette M., Fase-Fowler F., Borst P. The amplified H circle of methotrexate-resistant Leishmania tarentolae contains a novel P-glycoprotein gene. EMBO J. 1990, 9:1027-1033.
50. Pathak M.K., Yi T. Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine respondes in hemopoietic cell lines. J. Immunol. 2001, 167:3391-3397.
51. Roberts W.L., Rainey P.M. Antimony quantification in Leishmania by electrothermal atomic absorption spectroscopy. Anal. Biochem. 1993, 211:1-6.
52. Romero G.A.S., Guerra M.V.F., Paes M.G., Macedo V.O. Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate. Am. J. Trop. Med. Hyg. 2001, 65:456-465.
53. Sambrook J., Fritsch E.F., Maniatis T. Molecular Cloning: A Laboratory Manual 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor. second ed.
54. Sampaio M.C., Traub-Cseko Y.M. The 245 kb amplified chromosome of Leishmania (V.) braziliensis contains a biopterin transporter gene. Mem. Inst. Oswaldo Cruz 2003, 98:377-378.
55. Sereno D., Holzmuller P., Mangot I., Cuny G., Ouaissi A., Lemesre J.L. Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrob. Agents Chemother. 2001, 45:2064-2069.
56. Shaw J.J. Further thoughts on the use of the name Leishmania (Leishmania) infantum chagasi for the aetiological agent of American visceral leishmaniasis. Mem. Inst. Oswaldo Cruz 2006, 101:577-579.
57. Smith, C.L., Klco, S.R., Cantor, C.R., 1988. Pulsed-field electrophoresis and the technology of large DNA molecules. In: Davies, K.E., (Ed.), Genome Analysis, a pratical approach, IRL Press, Oxford, England. pp. 41-72.
58. 2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J. Biol. Chem. 2003, 278:25120-25132.
59. Sundar S., More D.K., Singh M.K., Singh V.P., Sharma S., Makharia A., Kumar P.C., Murray H.W. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin. Infect. Dis. 2000, 31:1104-1106.
60. Teixeira S.M. Control of gene expression in Trypanosomatidae. Braz. J. Med. Biol. Res. 1998, 31:1503-1516.
61. Torres D.C., Adaui V., Ribeiro-Alves M., Romero G.A., Arévalo J., Cupolillo E., Dujardin J.C. Targeted gene expression profiling in Leishmania braziliensis and Leishmania guyanensis parasites isolated from Brazilian patients with different antimonial treatment outcomes. Infect. Genet. Evol. 2010, 10:727-733.
62. Ubeda J.M., Légaré D., Raymond F., Ouamer A.A., Boisavert S., Rigault P., Corbeil J., Tremblay M.J., Olivier M., Papadopoulou B., Ouellette M. Modulation of gene expression in drug resistant Leishmania is associated with gene amplification gene deletion and chromosome aneuploidy. Genome Biol. 2008, 9:R115.
63. Ullman B. Multidrug resistance and P-glycoprotein in parasitic Protozoan. J. Bioenerg. Biomembr. 1995, 27:77-84.
64. Wang J., Brochu C., Wang X., Wang N., Ouellette M. Determination of trace antimony in cells by inductively coupled plasma mass spectrometry for drug resistance study of protozoan parasite. Chin. J. Anal. Lab. 2003, 22(suppl.):107-112.
65. White T.C., Fase-Fowler G., van Luenen H., Calafat J., Borst P. The H circles of Leishmania tarentolae are unique amplifiable system of oligomeric DNAs associated with drug resistance. J. Biol. Chem. 1988, 263:16977-16983.
66. World Health Organization. Strategic direction for leishmaniasis research: disease burden and epidemiological trends. Available at: (Last access 30.06.12). http://www.who.int/tdr/diseases/leish/direction/en/.
67. Wyllie S., Cunningham M.L., Fairlamb A.H. Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. J. Biol. Chem. 2004, 279:39925-39932.