Genetic Knockdown and Pharmacological Inhibition of Parasite Multidrug Resistance Transporters Disrupts Egg Production in Schistosoma mansoni
Figure 5
Administration of MDR inhibitors to S. mansoni-infected mice reduces host liver egg burden.
(A). Mean egg burden/g of liver (n = 3–5) from mice at 6–7 weeks post infection with approximately 200 cercariae, normalized to Control within each experiment. Mice were treated with 3 doses on alternating days of: diluted DMSO/Cremophore EL carrier (Control; white bar, n = 8); C-4 (50 mg/kg, n = 6); tariquidar (15 mg/kg, n = 3); dexverapamil (60 mg/kg, n = 3), or cyclosporin A (CSA, 60 mg/kg, n = 6). (B) Granulomas/cm2 found in livers of infected mice (n = 6) treated with carrier or drugs, as in A. (C) Mean ex vivo egg production (n = 4–6) from 3 pairs of adult parasites perfused from mice that were treated with the MDR inhibitors dexverapamil (60 mg/kg), C-4 (50 mg/kg), or cyclosporin A (CSA; 60 mg/kg) and subsequently cultured in RPMI for 48 h. Control represents eggs from parasites perfused from mice treated with carrier alone (diluted DMSO/Cremophore EL). Only CSA continues to disrupt egg production through the culture period. *, **, ***, and **** indicate P<0.05, P<0.01, P<0.001, and P<0.0001, respectively, unpaired, two-tailed t-tests.