Compound 1–Induced Slowing of Parasite Growth and BAG1 Expression Is Mediated by New Host Cell Gene Transcription

<div><p>(A) HFF cells were treated or co-treated for 3 h with 3 μM Compound 1 and 30 or 60 μM RNA polymerase II inhibitor DRB. Following removal of the compounds, VEG parasites were inoculated and BAG1 expression was evaluated 72 h postinfection. Antagonism of Compound 1 induction of parasite BAG1 with DRB shows a dose effect when comparing co-treatment with 30 or 60 μM DRB and 3 μM Compound 1 (DRB 30/C1 and DRB 60/C1, respectively). DRB alone had no effect on parasite growth or BAG1 expression, while induction by 3 μM Compound 1 (CMPND1) is included here for reference.</p><p>(B) In untreated cultures, VEG parasites reach greater than 70 per vacuole by 72 h postinfection (black circle), but vacuoles with an average of only four parasites were observed in Compound 1–treated cells (grey box). Co-treatment with 60 μM DRB restored parasite replication to approximately 60 parasites per vacuole (black box) by 72 h postinfection, while reducing the level of BAG1+ to 12% (dark bars) from greater than 70% in cultures treated with Compound 1 alone (light bars).</p>