Divergent Paths: CAP59 Gene Evolution in Cryptococcus and Implications for Pathogenicity

Document Type : Original Articles

Authors

1 Tikrit University

2 University of Anbar

10.22034/cmm.2024.345180.1496

Abstract

Background and purpose: C. neoformans and C. 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 examined CAP59 in both pathogenic and non-pathogenic species.

Material and Methods: The study identified Cryptococcus species through extensive literature, retrieved sequences from UniProt, explored protein families utilizing InterPro, MEME was used for motif analysis, multiple sequence alignment using Clustal Omega, performed the phylogenetic analysis with MEGA, modelled protein structures with MODELLER, and visualized pathogenic and non-pathogenic structures separately in PyMOL.

Results: 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 pathogenic species’ CAP59 gene sequence at highly conserved regions. The phylogenetic analysis and pairwise distance matrix revealed that C. amylolentus is closely related to pathogenic species. Predicted CAP59 protein structures were superimposed to show structural differences between pathogenic and non-pathogenic species.

Conclusion: In conclusion, this study suggests that non-pathogenic species may have evolved into pathogenic species because the CAP59 gene sequences of the non-virulent species were longer than the virulent species sequences, implying 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.

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