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Hybrid genome sequence of Cryptococcus neoformans of Indian origin and comparative genome analysis

Jananishree Sathiyamoorthy1, Jayapradha Ramakrishnan2

  • 1Actinomycetes Bioprospecting Lab, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, 613401, Tamilnadu, India.

Scientific Reports
|December 4, 2025
PubMed

Insights

This study presents the first complete genome sequence of an Indian Cryptococcus neoformans isolate, revealing key virulence genes and antifungal resistance markers. Understanding its genomic architecture is crucial for managing this neglected tropical disease.

Area of Science:

  • Genomics
  • Mycology
  • Infectious Diseases

Background:

  • Cryptococcus neoformans (C. neoformans) is an opportunistic fungus causing severe pneumonia and meningitis globally.
  • Despite reduced incidence, C. neoformans infections remain a significant health concern with high mortality rates, classified as a neglected tropical disease.
  • Elucidating the genomic basis of C. neoformans virulence and antifungal resistance is essential for improved disease management.

Purpose of the Study:

  • To perform the first comprehensive genomic analysis of an Indian Cryptococcus neoformans isolate.
  • To investigate the virulome, resistome, and genomic variations, including Single Nucleotide Polymorphisms (SNPs).
  • To conduct phylogenomic and pan-genome analyses to understand evolutionary relationships and genomic dynamics.

Main Methods:

  • Whole-genome sequencing of an Indian C. neoformans isolate (subsp. grubii).
  • Comparative virulome analysis with reference strains (Cn, H99, JEC21).
  • Whole-genome SNP analysis for hypermutator categorization, phylogenomic, and pan-genome analysis.

Main Results:

  • The Indian isolate genome contains 4.8% virulence genes; comparative analysis identified shared crucial virulence genes across strains.
  • All analyzed strains possess antifungal resistance (AFR) genes, though specific AFR-defining SNPs were largely absent.
  • SNP analysis classified strains as hyper- or non-hypermutators; phylogenomic and pan-genome analyses confirmed a shared core genome and revealed gene expansion/contraction.

Conclusions:

  • This study provides the first in-depth genomic insights into an Indian C. neoformans isolate, integrating genetic variation, virulome, and resistome data.
  • The findings underscore the importance of comparative genomics and bioinformatic tools for analyzing fungal pathogens like C. neoformans.
  • Understanding the genomic landscape of C. neoformans is critical for developing effective strategies against this neglected tropical disease.
Keywords:
Cryptococcus neoformans sp.Comparative genomicsPan-genomePhylogenyResistomeVirulome

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