Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement.
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.
Castanys-Muñoz
Esther
E
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain.
Pérez-Victoria
José María
JM
Gamarro
Francisco
F
Castanys
Santiago
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000634:Aminoquinolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D001693:Biological Transport, Active; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D005456:Fluorescent Dyes; D017125:Genes, Protozoan; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology*; D008051:Lipid Bilayers / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014170:Transformation, Genetic
D018528:ATP-Binding Cassette Transporters; D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D010767:Phosphorylcholine; C039128:miltefosine; D002738:Chloroquine; C080436:8-aminoquinoline