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13. Advances in leishmaniasis

Author

Murray, Henry W., Berman, Jonathan D., Davies, Clive R., and Saravia, Nancy G.

Subjects
Leishmaniasis -- Care and treatment, Leishmaniasis -- Causes of, Leishmaniasis -- Physiological aspects, Leishmaniasis -- Diagnosis
Published
2005

14. Social innovation in global health: sparking location action

Author

Halpaap, Beatrice M, primary, Tucker, Joseph D, additional, Mathanga, Don, additional, Juban, Noel, additional, Awor, Phyllis, additional, Saravia, Nancy G, additional, Han, Larry, additional, de Villiers, Katusha, additional, Kitamura, Makiko, additional, Cuervo, Luis Gabriel, additional, Peeling, Rosanna, additional, and Reeder, John C, additional

Published
2020
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21. An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections

Author

Saldarriaga, Omar A., primary, Castellanos-Gonzalez, Alejandro, additional, Porrozzi, Renato, additional, Baldeviano, Gerald C., additional, Lescano, Andrés G., additional, de Los Santos, Maxy B., additional, Fernandez, Olga L., additional, Saravia, Nancy G., additional, Costa, Erika, additional, Melby, Peter C., additional, and Travi, Bruno L., additional

Published
2016
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22. Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis

Author

Rosales-Chilama, Mariana, primary, Gongora, Rafael E., additional, Valderrama, Liliana, additional, Jojoa, Jimena, additional, Alexander, Neal, additional, Rubiano, Luisa C., additional, Cossio, Alexandra, additional, Adams, Emily R., additional, Saravia, Nancy G., additional, and Gomez, María Adelaida, additional

Published
2015
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24. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

Author

Ramírez, Carolina, primary, Díaz-Toro, Yira, additional, Tellez, Jair, additional, Castilho, Tiago M., additional, Rojas, Ricardo, additional, Ettinger, Nicholas A., additional, Tikhonova, Irina, additional, Alexander, Neal D., additional, Valderrama, Liliana, additional, Hager, Janet, additional, Wilson, Mary E., additional, Lin, Aiping, additional, Zhao, Hongyu, additional, Saravia, Nancy G., additional, and McMahon-Pratt, Diane, additional

Published
2012
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49. Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantumAxenic and Intracellular Amastigotes

Author

El Fadili, Karima, Messier, Nadine, Leprohon, Philippe, Roy, Gaétan, Guimond, Chantal, Trudel, Nathalie, Saravia, Nancy G., Papadopoulou, Barbara, Légaré, Danielle, and Ouellette, Marc

Abstract

ABSTRACTAntimonial compounds are the mainstay for the treatment of infections with the protozoan parasite Leishmania. We present our studies on Leishmania infantumamastigote parasites selected for resistance to potassium antimonyl tartrate [Sb(III)]. Inside macrophages, the Sb(III)-selected cells are cross-resistant to sodium stibogluconate (Pentostam), the main drug used against Leishmania. Putative alterations in the level of expression of more than 40 genes were compared between susceptible and resistant axenic amastigotes using customized DNA microarrays. The expression of three genes coding for the ABC transporter MRPA (PGPA), S-adenosylhomocysteine hydrolase, and folylpolyglutamate synthase was found to be consistently increased. The levels of cysteine were found to be increased in the mutant. Transfection of the MRPAgene was shown to confer sodium stibogluconate resistance in intracellular parasites. This MRPA-mediated resistance could be reverted by using the glutathione biosynthesis-specific inhibitor buthionine sulfoximine. These results highlight for the first time the role of MRPA in antimony resistance in the amastigote stage of the parasite and suggest a strategy for reversing resistance.

Published
2005
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50. Antimony Uptake Systems in the Protozoan Parasite Leishmaniaand Accumulation Differences in Antimony-Resistant Parasites

Author

Brochu, Christian, Wang, Jingyu, Roy, Gaétan, Messier, Nadine, Wang, Xiao-Yan, Saravia, Nancy G., and Ouellette, Marc

Abstract

ABSTRACTThe first line drug against leishmaniasis consists of pentavalent antimony [Sb(V)], but there is general belief that the active form of the metal is the trivalent form [Sb(III)]. In this study, we have quantified the accumulation of Sb(V) and Sb(III) in Leishmaniaby using inductively coupled plasma mass spectrometry. The accumulation was studied in three Leishmaniaspecies at various life stages, sensitive or resistant to antimony. Both Sb(III) and Sb(V) are accumulated in promastigote and amastigote parasites, but through competition experiments with arsenite, we found that the routes of entry of Sb(V) and Sb(III) are likely to differ in Leishmania. The level of accumulation of either Sb(III) or Sb(V), however, was not correlated with the susceptibility of wild-type Leishmaniacells to antimony. This suggests that other factors may also be implicated in the mode of action of the drugs. In contrast to metal susceptibility, resistance to Sb(III) correlated well with decreased antimony accumulation. This phenotype was energy dependent and highlights the importance of transport systems in drug resistance of this protozoan parasite.

Published
2003
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