The pre-mRNA Splicing Modulator Pladienolide B Inhibits Cryptococcus neoformans Germination and Growth

Cryptococcus neoformans is an opportunistic fungal pathogen responsible for life-threatening infections, particularly in immunocompromised individuals. We investigated the efficacy of a human splicing inhibitor, pladienolide B (PladB), as an antifungal against C. neoformans. PladB inhibited growth of C. neoformans and spore germination. The potency of PladB could be increased by simultaneous treatment with either FK506 or clorgyline. This combination treatment significantly reduced fungal growth and prevented spore germination. We used paired-end RNA-seq analysis to investigate resultant gene expression and alternative splicing changes from exposure to these drugs.