Divergent paths: CAP59 gene evolution in Cryptococcus and implications for pathogenicity

Cryptococcus neoformans and Cryptococcus gattii are highly virulent species that cause diseases, such as meningoencephalitis and pulmonary infections. The CAP59 gene predominantly determines the virulence of the pathogenic species. This study aimed to examine CAP59 in both pathogenic and non-pathogenic species.

This study identified Cryptococcus species through extensive literature, retrieved sequences from UniProt, explored protein families utilizing InterPro, motif analysis by MEME, multiple sequence alignment using Clustal Omega, performance of the phylogenetic analysis with MEGA, modeled protein structures with MODELLER, and separately visualized pathogenic and non-pathogenic structures in PyMOL.

Motif analysis showed four conserved regions between the pathogenic and non-pathogenic sequences. Moreover, multiple sequence alignment revealed that pathogenic CAP59 gene sequences lacked a significant portion, compared to non-pathogenic ones, with several mutations in the gene sequence of pathogenic species CAP59 at highly conserved regions. The phylogenetic analysis and pairwise distance matrix revealed that Cryptococcus amylolentus is closely related to pathogenic species. Predicted CAP59 protein structures were superimposed to show structural differences between pathogenic and non-pathogenic species.

In conclusion, the results suggested that non-pathogenic species may have evolved into pathogenic species since the CAP59 gene sequences of the non-virulent species were longer than those of the virulent species sequences. It implies that the virulent sequences may have lost that region at some point in evolution, which additional research on capsule formation-related genes can further corroborate.