Abstract
Leishmaniasis treatment is hampered by the increased appearance of treatment failure. ATP-binding cassette (ABC) transporters are usually involved in drug resistance both in tumor cells and in microorganisms. Here we report the characterization of an ABCG-like transporter, LiABCG6, localized mainly at the plasma membrane in Leishmania protozoan parasites. When overexpressed, this half-transporter confers significant resistance to the leishmanicidal agents miltefosine and sitamaquine. This resistance phenotype is mediated by a reduction in intracellular drug accumulation. LiABCG6 also reduces the accumulation of short-chain fluorescent phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. As a whole, these results suggest that LiABCG6 could be implicated in phospholipid trafficking and drug resistance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Aminoquinolines / chemistry
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Aminoquinolines / metabolism
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Aminoquinolines / pharmacology
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Animals
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Antiprotozoal Agents / chemistry
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Antiprotozoal Agents / metabolism
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Antiprotozoal Agents / pharmacology
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Base Sequence
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Biological Transport, Active
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Chloroquine / metabolism
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Chloroquine / pharmacology
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DNA, Protozoan / genetics
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Drug Resistance / genetics
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Drug Resistance / physiology
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Fluorescent Dyes
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Genes, Protozoan
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Humans
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Leishmania infantum / drug effects*
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Leishmania infantum / genetics
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Leishmania infantum / metabolism*
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Leishmaniasis, Visceral / drug therapy*
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Leishmaniasis, Visceral / parasitology*
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Lipid Bilayers / metabolism
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Phosphorylcholine / analogs & derivatives
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Phosphorylcholine / metabolism
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Phosphorylcholine / pharmacology
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Protozoan Proteins / genetics
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Protozoan Proteins / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transformation, Genetic
Substances
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ATP-Binding Cassette Transporters
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Aminoquinolines
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Antiprotozoal Agents
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DNA, Protozoan
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Fluorescent Dyes
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Lipid Bilayers
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Protozoan Proteins
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Recombinant Proteins
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Phosphorylcholine
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miltefosine
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Chloroquine
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8-aminoquinoline