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Antimicrobial Agents and Chemotherapy, October 2008, p. 3573-3579, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00587-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Characterization of an ABCG-Like Transporter from the Protozoan Parasite Leishmania with a Role in Drug Resistance and Transbilayer Lipid Movement{triangledown}

Esther Castanys-Muñoz, José María Pérez-Victoria, Francisco Gamarro,* and Santiago Castanys*

Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain

Received 5 May 2008/ Returned for modification 4 June 2008/ Accepted 11 July 2008

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.

* Corresponding author. Mailing address: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain. Fax: 34 958 181632. Phone for Santiago Castanys: 34 958 181666. E-mail: castanys{at}ipb.csic.es. Phone for Francisco Gamarro: 34 958 181667. E-mail: gamarro{at}ipb.csic.es

{triangledown} Published ahead of print on 21 July 2008.

Antimicrobial Agents and Chemotherapy, October 2008, p. 3573-3579, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00587-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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