Ultrastructural Features of Cryptococcus neoformans Histone Deacetylases Null Mutant Strains

Cryptococcus neoformans is a pathogen affecting predominantly immunocompromised individuals. Epigenetic regulation is pivotal for controlling C. neoformans virulence traits. Null mutants of histone deacetylase (HDAC) genes demonstrate reduced virulence. Here, we employed scanning (SEM) and transmission electron microscopy (TEM) to examine the ultrastructure of C. neoformans HDA1 and HOS2 null mutant strains. SEM revealed unipolar budding in the H99, hda1∆ and hos2∆ strains, whereas the hda1∆hos2∆ double mutant displayed evident multipolar budding. The hos2∆ strain exhibited defective capsule. TEM analysis showed a thicker cell wall for hda1∆ in comparison to H99, while the hos2∆ and hda1∆hos2∆ mutants displayed thinner cell walls. The hos2∆ and hda1∆/hos2∆ strains exhibited mitochondrial swelling. The hda1∆hos2∆ mutant also presented morphological features suggestive of cell degeneration. These findings highlight the critical role of HDACs in C. neoformans morphogenesis, which is essential to host cell-yeast interaction.

The online version contains supplementary material available at 10.1007/s12088-025-01533-5.