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

Human opportunistic fungi C. neoformans are a global health concern as they cause severe pneumonia and cryptococcal meningitis in tropical and subtropical regions. Though the occurrence of infection has reduced from 2014 to 2022, the mortality rate remains high, and it is considered a neglected tropical disease. More studies are needed to elucidate the genomic architecture and functional traits required to underpin the disease management of Cryptococcus neoformans. This study showcases the first complete genome sequence of an Indian isolate of Cryptococcus, identified as subsp. grubii containing 4.8% of virulence genes in a total genome. A comparative virulome analysis revealed that study genomes Cn, H99 and JEC21 harbor crucial virulence genes associated with infection severity. While all study strains possess genes promoting antifungal resistance (AFR), most lack specific SNPs defining AFR. The whole genome Single Nucleotide Polymorphism (SNP) analysis categorized the strains as hyper- and non-hypermutators. The phylogenomic and pan-genome analysis revealed that the study strains share a core genome, highlighting evolutionary relatedness. The study shows gene expansion and contraction between the study strains. This pioneering study presents Cryptococcus's first comprehensive genomic analysis from India, integrating genetic variations, virulome, resistome, and pan-genome dynamics. The study highlights the necessity of bioinformatic tools for efficient genome analysis and large-scale comparative genome research.