In-silico Studies on Virulence Factors of Cryptococcus Species: Phylogenetic Analysis and B-cell Epitope Prediction

Abstract

Virulence proteins ensure the survival of Cryptococcus in its host. The epitopes present in these virulence factors can modulate the host's immune system and contribute tocryptococcosis's pathobiology significantly. The amino acid sequences of virulence factors (glucuronoxylomannan (GXM), superoxide dismutase (SOD), mannoprotein (MP), urease, CAP binding protein, galactoxylomannan (GalXM), phospholipase-B, and laccase) of C. neoformans, C. n. grubii, and C. gattii were retrieved from NCBI. Analyses of the phylogenetic relationship between virulence factors were performed by using PhyML software and JMP 13.1 software. Further, ABCpred, BCPred, BcePred web servers were employed for the prediction of linear B-cell epitopes in amino acid sequences of said virulence factors. In all the three Cryptococcus species, laccase, CAP binding protein, and mannoprotein were highly conserved compared to GalXM, GXM, and SOD virulence factors. Superoxide dismutase (SOD) with the lowest gamma distribution value is considered to be highly adaptable. Further, the maximum number of B-cell epitopes was observed on the urease of C. n. grubii. In due course of time, Cu, Zn Superoxide dismutase (SOD) might play the main role in Cryptococcus species' pathogenicity due to its highly variable nature. Additionally, urease could be used to design epitope-based anti-cryptococcal drugs. Nonetheless, the results of this in-silico study need wet lab validation.