NDLI: Experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of Leishmania donovani and L. infantum

Content Provider	Springer Nature Link
Author	Hendrickx, S. Boulet, G. Mondelaers, A. Dujardin, J. C. Rijal, S. Lachaud, L. Cos, P. Delputte, P. Maes, L.
Copyright Year	2014
Abstract	Although widespread resistance of Leishmania donovani and L. infantum against miltefosine (MIL) and paromomycin (PMM) has not yet been demonstrated, both run the risk of resistance selection. Unraveling the dynamics and mechanisms of resistance development is key to preserve drug efficacy in the field. In this study, resistance against PMM and MIL was experimentally selected in vitro in intracellular amastigotes of several strains of both species with different antimony susceptibility background. To monitor amastigote susceptibility, microscopic determination of IC50-values and promastigote back-transformation assays were performed. Both techniques were also used to evaluate the susceptibility of field isolates from MIL-relapse patients. PMM-resistance could readily be selected in all species/strains, although promastigotes remained fully PMM-susceptible. Successful MIL-resistance selection was demonstrated only by promastigote back-transformation at increasing MIL-concentrations upon successive selection cycles. Important to note is that amastigotes with the MIL-resistant phenotype could not be visualized after Giemsa staining; hence, MIL-IC50-values showed no shift. The same phenomenon was observed in a set of recent clinical isolates from MIL-relapse patients. This study clearly endorses the need to use intracellular amastigotes for PMM- and MIL-susceptibility testing. When monitoring MIL-resistance, promastigote back-transformation should be used instead of the standard Giemsa staining. In-depth exploration of the mechanistic background of this finding is warranted.
Starting Page	1875
Ending Page	1881
Page Count	7
File Format	PDF
ISSN	09320113
Journal	Parasitology Research
Volume Number	113
Issue Number	5
e-ISSN	14321955
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-03-11
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	In vitro Promastigote back-transformation Giemsa Medical Microbiology Microbiology Immunology
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Veterinary Parasitology Insect Science

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