Fig. 4: βOHB disrupted transcriptional processes in P. falciparum 3D7 parasites.
a, Volcano plot showing that βOHB affects genome-wide transcription in P. falciparum 3D7 parasites during intraerythrocytic development. The genes associated with the early development and erythrocyte invasion of parasites were mostly affected. Genes with a |log2(FC)| ≥ 0.25 and Padj < 0.05 are shown. Parasite genes at various developmental stages are colour-coded, with arrows pointing to specific genes. Developmental stages are colour-coded. b–i, Bar charts of DEGs in the merozoite stage showing that the transcription of WD repeat-containing proteins (b) and proteins that function in trafficking (c), liver and sexual stages (d) and pre-mRNA splicing (e) was upregulated after exposure to βOHB, and the transcription of genes related to MSP (f), erythrocyte adhesion (g), locomotion (h) and development (i) was downregulated. Brown indicates upregulated genes; dark green indicates downregulated genes. Genes with a |log2(FC)| ≥ 0.15 and Padj < 0.05 are shown. Detailed information is provided in Supplementary Table 14. j, KEGG enrichment column showing that invasion, motility and post-translational ubiquitin-dependent process pathways were significantly downregulated in the merozoites of P. falciparum 3D7 exposed to βOHB. k, KEGG enrichment column showing that invasion, motility and post-translational ubiquitin-dependent process pathways were significantly downregulated in the early ring stage of P. falciparum 3D7 after exposure to βOHB. Detailed information is shown in Supplementary Tables 16 and 17. l, Western blotting results show that βOHB significantly reduced the expression of MSP1 and MYC-tagged MTIP, and NAD replenishment restored the βOHB-mediated suppression in the expression of these proteins. However, we failed to detect ApiAP2 (PF3D7_0420300) in western blot assays, probably because of its ultra-high molecular weight. Representatives of three independently repeated experiments with similar results. Statistical comparisons between groups were performed using two-sided Wilcoxon rank-sum tests (a–k).
