Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni
Fig 2
LSD1 inhibition is detrimental to Schistosoma mansoni survival.
(A). Simplified scheme of the acquisition of the two developmental stages of the parasite used in this study. Cercariae were harvested from infected snails and used to either infect hamsters or mechanically transformed into schistosomula for in vitro culture. Hamsters were perfused 42–49 days postinfection to harvest adult worm pairs. (B). The relative ATP dosage (%) of schistosomula treated with 25 μM MC3935 (green line) was measured every 24 h (up to 96 h). Schistosomula given DMSO or nothing are shown in gray and black lines, respectively. (C) Relative ATP dosage (%) of adult worm pairs treated with 25 μM MC3935 for 96 h. NT, nontreated adult worm pairs. The results of three independent experiments are shown, and error bars represent the standard deviation (SD). (D) Evaluation of the viability of adult worm treated with DMSO or 25 μM MC3935 for 96 h. Several parameters of adult worm viability were monitored daily until day 4, using an optical microscope equipped with a digital camera. Details for these classifications are described in the methods section. These viability parameters were reviewed and scored by two independent observers. Videos of the control or MC3935-treated worms to confirm the described scores are available (in Supplementary videos). Statistical significance, comparing MC3935-treated and vehicle conditions, was determined using Student´s t-test, with ****p<0.0001.