Expression of ATP-binding cassette multidrug transporters in the giant liver fluke Fasciola gigantica and their possible involvement in the transport of bile salts and anthelmintics.
ATP-binding cassette (ABC) transporters belong to one of the largest protein families that either import or export a wide spectrum of different substrates. Certain members of this superfamily have been implicated in multidrug resistance in various types of cancer as well as in pathogenic microorganisms. The role of ABC proteins in parasitic multidrug resistance becomes increasingly evident. However, studies on ABC transporters in helminths have been limited to MDR1 and MRP orthologues. In the present study, we reported, for the first time, the expression and localization of ABC proteins including orthologues of MDR1, MRP1, BCRP, and BSEP in the giant liver fluke Fasciola gigantica. Furthermore, the functional activities of these ABC transporters were characterized in isolated fluke cells using a fluorescent substrate, rhodamine. The results revealed the inhibition of rhodamine efflux by cyclosporin A, a potent inhibitor of ABC transporters. Interestingly, our data suggested that these proteins might play a role in the export of bile salts, in particular, taurocholate. Although, we did not observe any substantial changes in rhodamine transport in the presence of anthelmintics under experimental conditions, however, our findings altogether shed light on the possible involvement of several members of ABC proteins in the mechanism of drug resistance as well as detoxification process in helminths to survive inside their hosts.
Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Supeecha
S
Kumkate
Supatra
S
Chunchob
Tavan
T
Janvilisri
D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002417:Cattle; D005209:Fasciola / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D012235:Rhodamines / Q000378:metabolism
D000871:Anthelmintics; D001647:Bile Acids and Salts; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012235:Rhodamines