Role of P glycoprotein in the course and treatment of Encephalitozoon microsporidiosis.
Encephalitozoon microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the Encephalitozoon microsporidia, E. cuniculi, E. hellem, and E. intestinalis, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species.
Leitch
G J
GJ
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. Leitch@msm.edu
Scanlon
M
M
Shaw
A
A
Visvesvara
G S
GS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D015766:Albendazole / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016572:Cyclosporine / Q000494:pharmacology; D016819:Encephalitozoon / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016890:Encephalitozoonosis / Q000503:physiopathology* / Q000628:therapy*; D005452:Fluoresceins / Q000378:metabolism; D019450:Genes, MDR / Q000235:genetics; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000871:Anthelmintics; D002121:Calcium Channel Blockers; D005452:Fluoresceins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014700:Verapamil; D015766:Albendazole; C007740:fluorexon