Abstract
In the present study, the gene expression of three multidrug resistance (MDR) and resistance-associated protein (MRP) transport proteins or efflux pumps was characterized and the phenotypic evidence for such pumps was demonstrated in cultured Madin-Darby canine kidney (MDCK) cells. A gradient for the fluorescent probe calcein was established between parasite and host cell suggestive of a parasite extrusion pump at the parasite-host interface. This gradient was decreased in a glucose-free medium containing 2-deoxyglucose or 3-O-methylglucose, by probenecid, and by the isoflavonoid, narigenin, suggesting that the calcein extrusion was energy-dependent and involved an MRP-like pump. While neither MDR or MRP inhibiters significantly affected transcript levels of any of the ABC transporters, transcript levels of the Cryptosporidium parvum ABC protein (CpABC1), an MRP transporter, were consistently expressed 4 logs higher than either CpABC3 or CpABC2, suggesting a prominent role in the intracellular stages of the parasite.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3-O-Methylglucose / pharmacology
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Animals
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Cryptosporidium parvum / drug effects*
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Cryptosporidium parvum / genetics
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Cryptosporidium parvum / metabolism
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Cyclosporine / pharmacology*
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Deoxyglucose / pharmacology
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Drug Resistance, Multiple / drug effects
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Drug Resistance, Multiple / genetics
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Flavanones / pharmacology
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Fluoresceins
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Fluorescent Dyes
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Gene Expression / drug effects
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Multidrug Resistance-Associated Proteins / antagonists & inhibitors
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Probenecid / pharmacology*
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Verapamil / pharmacology*
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Flavanones
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Fluoresceins
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Fluorescent Dyes
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Multidrug Resistance-Associated Proteins
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3-O-Methylglucose
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Cyclosporine
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Deoxyglucose
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Verapamil
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naringenin
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Probenecid
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fluorexon