Characterization of Leishmania (Leishmania) amazonensis promastigotes resistant to pentamidine

Pentamidine is a second-line agent used in the treatment of leishmaniasis and its mode of action and mechanism of resistance is not well understood. It was previously demonstrated that transfection of promastigotes and amastigotes with the ABC transporter PRP1 gene confers resistance to pentamidine....

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Veröffentlicht in:	Experimental parasitology 2008-09, Vol.120 (1), p.98-102
Hauptverfasser:	Coelho, Adriano C., Gentil, Luciana G., da Silveira, José Franco, Cotrim, Paulo C.
Format:	Artikel
Sprache:	eng
Schlagworte:	4′,6′-diamidino-2-phenylindole ABC ABC transporter Animals Antiprotozoal Agents - pharmacology ATP-binding cassette ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - physiology Biological and medical sciences Blotting, Southern DAPI DNA, Protozoan - chemistry DNA, Protozoan - isolation & purification Drug resistance Drug Resistance - genetics Electrophoresis, Gel, Pulsed-Field Fluorescent Dyes Fundamental and applied biological sciences. Psychology Indoles Inhibitory Concentration 50 kilobase Leishmania Leishmania amazonensis Leishmania mexicana - drug effects Leishmania mexicana - genetics Life cycle. Host-agent relationship. Pathogenesis megabase Microscopy, Fluorescence Mutation PATH Pentamidine Pentamidine - pharmacology pentamidine resistance protein 1 Phenotype potassium antimonyl tartrate trihydrate Protozoa Protozoan Proteins - genetics Protozoan Proteins - physiology PRP1
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Beschreibung
Zusammenfassung:	Pentamidine is a second-line agent used in the treatment of leishmaniasis and its mode of action and mechanism of resistance is not well understood. It was previously demonstrated that transfection of promastigotes and amastigotes with the ABC transporter PRP1 gene confers resistance to pentamidine. To further clarify this point, we generated Leishmania amazonensis mutants resistant to pentamidine. Our results indicated that this ABC transporter is not associated with pentamidine resistance in lines generated by drug pressure through amplification or overexpression mechanisms of PRP1 gene.
ISSN:	0014-4894 1090-2449
DOI:	10.1016/j.exppara.2008.03.018