title: A novel ATP-binding cassette transporter, ABCG6 is involved in chemoresistance of Leishmania.
abstract: ATP-binding cassette (ABC) transporters constitute the biggest family of membrane proteins involved in drug resistance and other biological activities. Resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries and in many instances it is due to overexpressed ABC efflux pumps. Progressively adapted camptothecin (CPT)-resistant parasites show overexpression of a novel ABC transporter, which was classified as ABCG6. Transfection and overexpression of LdABCG6 in wild type parasites, shows its localization primarily in the plasma membrane and flagellar pocket region. Overexpressed LdABCG6 confers substantial CPT resistance to the parasites by rapid drug efflux. Various inhibitors have been tested for their ability to revert the CPT-resistant phenotype to specifically understand the inhibition of LdABCG6 transporter. Transport experiments using everted membrane vesicles were carried out to gain an insight into the kinetics of drug transport. This study provides further knowledge of specific membrane traffic ATPase and its involvement in the chemoresistance of Leishmania.
authors.affiliation: Department of Molecular Parasitology, Infectious Disease Group, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
authors.forename: Somdeb
authors.initials: S
authors.lastname: BoseDasgupta
authors.forename: Agneyo
authors.initials: A
authors.lastname: Ganguly
authors.forename: Amit
authors.initials: A
authors.lastname: Roy
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Mukherjee
authors.forename: Hemanta K
authors.initials: HK
authors.lastname: Majumder
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001693:Biological Transport, Active; D002166:Camptothecin / Q000494:pharmacology*; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D021261:Parasitic Sensitivity Tests; D015800:Protozoan Proteins / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D002166:Camptothecin