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Drug Resistance in Leishmania

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Abstract

Protozoan parasites of the genus Leishmania cause a wide range of diseases affecting 12 million people worldwide with 1.5–2 million new cases each year. With no vaccine available yet, the control of these parasites relies solely on chemotherapy. Low-cost antimony-derived compounds remain the primary antileishmanial treatment in most developing countries. Increasing drug resistance towards these molecules has forced the use of alternative therapies in highly endemic areas including amphotericin B, paromomycin, and miltefosine. This chapter is presenting our current understanding of the mode of action and underlying resistance mechanisms of the few therapeutic drugs used against Leishmania.

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Abbreviations

AMB:

Amphotericin B

CL:

Cutaneous leishmaniasis

DCL:

Diffuse cutaneous leishmaniasis

GSH:

Glutathione

MCL:

Mucocutaneous leishmaniasis

MIL:

Miltefosine

PKDL:

Post-kala-azar dermal leishmaniasis

PM:

Paromomycin

SAG:

Sodium antimony gluconate

SbIII :

Trivalent antimonials

SbV :

Pentavalent antimonials

SILAC:

Stable isotope labeling by amino acids in cell culture

TSH:

Trypanothione

VL:

Visceral leishmaniasis

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Acknowledgments

The authors are grateful to the members of the laboratory at the Centre de Recherche en Infectiologie du CHU de Québec for their dedication, professionalism, and critical reading of the manuscript. The authors owe an apology to their colleagues in the field of leishmaniasis and even wider area of drug resistance whose work could not be properly acknowledged due to space limitations. This work was funded by a CIHR grant to M.O. M.O. holds the Canada Research Chair in Antimicrobial Resistance.

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Authors and Affiliations

  1. Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec, Pavillon CHUL and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, 2705 boul. Laurier, G1V 4G2, QC, Canada

    Danielle Légaré & Marc Ouellette

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  1. Danielle Légaré
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  2. Marc Ouellette
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Correspondence to Marc Ouellette .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Albert Berghuis

  2. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Greg Matlashewski

  3. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Mark A. Wainberg

  4. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Donald Sheppard

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Légaré, D., Ouellette, M. (2017). Drug Resistance in Leishmania . In: Berghuis, A., Matlashewski, G., Wainberg, M., Sheppard, D. (eds) Handbook of Antimicrobial Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0694-9_17

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