Role of P Glycoprotein in the Course and Treatment of Encephalitozoon Microsporidiosis

Abstract

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 antimultidrug 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.

Comparative analysis of sequences encoding ABC systems in the genome of the microsporidian Encephalitozoon cuniculi

“…The lack of such sequences is also supported by the analysis of conserved motifs (data not shown). However, immuno£uorescence images of Encephalitozoon-infected mammalian cells obtained after reaction with anti-P-gp antibodies showed signi¢cant labeling of merogonial parasite stages adjacent to the parasitophorous vacuole, where Encephalitozoon cells are known to proliferate [4]. The question whether that labeling was due to host or parasite P-gp is still an open question.…”

“…In the case of microsporidia, an immuno£uorescence study supported the association of P-gp epitopes with the cell surface of Encephalitozoon developing stages [4]. Verapamil and cyclosporin A were shown to act as chemosensitizing agents for albendazole, suggesting that the e¡ective-ness of this drug may be increased through the inhibition of P-gp pump activity [4].…”

Nematodes as Models for the Study of the Regulation of Activity of Pglycoproteins in Multidrug Resistance (MDR)

“…VPL and CsA acted as chemosensitizing agents for the in vitro infection assay of the antiparasitic drug albendazole. These observations suggest that inhibiting host cell pumps and possibly parasite MDR pumps increases the efficacy of antiparasitic agents in these and other microsporidia species [141].…”

“…These protozoa proliferate and differentiate within a parasitophorous vacuole inside host cells [141]. Both immunocytochemistry and the fluorescence assay detected Pgp, but not MRP, in both the host cells and the developing stages of the parasite.…”

Biotic activity of Ca2+-modulating non-traditional antimicrobial and -viral agents

“…In turn, these processes, directed by identical toxin concentrations used for trypanosome benefit, can present formidable obstacles to other infectious agents, including convergent trypanosome strains (Ulrich and Schmid-Hempel, 2012) and possible Encephalitozoon (cf. Leitch et al, 2001) and Toxoplasma parasites (cf. Meirelles and De Souza, 1983), which compete for limited shared host resources and/or must overcome toxin-modified host immunoresponses.…”