MSACL 2026 Abstract

Integrated Genomic and Metabolic Profiling of Cryptococcus neoformans Reveals Virulence‑Associated Pathways Relevant to Cryptococcal Meningitis

Raiha Fatima (1), Kaleem Imdad (2)
COMSATS University Islamabad, Department of Biosciences, Pakistan

Raiha Fatima, Master of Science (Presenter) COMSATS University Islamabad, Pakistan

Relevant Financial Disclosures (within past 24 months, reported on Jun 26, 2026) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
Cryptococcus neoformans is an encapsulated fungal pathogen responsible for life-threatening cryptococcal meningitis, particularly in immunocompromised individuals. Its ability to invade the central nervous system and cross the blood–brain barrier is driven by complex genetic and metabolic adaptations that remain incompletely understood. A deeper understanding of its genomic architecture and functional pathways is essential for identifying mechanisms of virulence and potential therapeutic targets.

METHODS:
Whole genome sequencing was performed on clinical isolates of C. neoformans using Illumina sequencing technology. High-quality genome assemblies were generated and subjected to comprehensive functional annotation. Bioinformatics analyses included antiSMASH for secondary metabolite biosynthetic gene cluster prediction, KEGG and KOBAS for pathway enrichment analysis, and InterPro along with BlastKOALA for protein function classification and metabolic reconstruction. Comparative genomic approaches were applied to evaluate structural and functional conservation.

RESULTS:
The assembled genome exhibited a size of approximately 19.1 Mb distributed across 14 chromosomes, consistent with reference genomes of C. neoformans. Functional annotation revealed conserved metabolic pathways alongside distinct secondary metabolite biosynthetic gene clusters, including NRPS-like and terpene-associated clusters, suggesting potential roles in virulence-associated metabolite production. Pathway analysis further identified host-interactive signaling networks, including IL-17 and VEGF-associated pathways, which may contribute to immune modulation and fungal survival under host stress conditions.

CONCKUSION:
This study provides an integrated genomic and in-silico metabolic framework for understanding C. neoformans pathogenicity. The identification of virulence-associated biosynthetic clusters and host-interactive pathways highlights potential targets for future antifungal therapeutic strategies and biomarker development. These findings contribute to a systems-level understanding of fungal infection mechanisms relevant to cryptococcal meningitis.