Transcriptomics Insights into Targeting CK2 Complex in Cryptococcus neoformans: Implications for Large-Scale Antifungal Virtual Screening

TL;DR

This study explores the role of the CK2 complex in the fungus Cryptococcus neoformans and identifies potential antifungal drugs using transcriptomics and computational screening.

Contribution

The study introduces a novel approach combining transcriptomics and virtual screening to identify FDA-approved drugs targeting CK2 complex in Cryptococcus neoformans.

Findings

RNA-sequencing identified 936-1159 dysregulated genes in Ck2 mutant strains of Cryptococcus neoformans.

STRING and Cytoscape analyses revealed key hub genes and protein interactions affected by Ck2 mutations.

Three FDA-approved drugs (amphotericin B, idarubicin, and candicidin) were identified as potential CK2 complex inhibitors.

Abstract

Cryptococcus neoformans is a pathogenic fungus that causes fungal meningitis and other infections in immunocompromised patients. The casein kinase 2 (Ck2) complex regulates
cellular processes. This study provides transcriptomics and functional insights into the Ck2 complex and other pathogenic proteins of Cryptococcus neoformans as therapeutic targets.

The study used computational methods to explore the transcriptomic and functional aspects of the Ck2 complex and other pathogenic proteins in Cryptococcus neoformans. RNA-sequencing analysis of control and experimental cell cultures under three different conditions (cka1Δ mutant vs wild, ckaΔ, ckb1Δ, ckb2Δ [triple] mutants vs wild, and wild vs all mutants) was performed, followed by the STRING analysis of the dysregulated genes to identify the protein-protein interactions, while Cytoscape was used to identify the hub genes in all three conditions.

The RNA-sequencing analysis resulted in various dysregulated genes such as 936 (cka1Δ mutant vs wild), 1154 (triple vs wild), and 1159 (wild vs all mutants). Cellular components, molecular functions, and KEGG pathways in three conditions. The hub genes that elevated the most, Q5KFT2_CRYNJ, ARO1_CRYNJ, Q5KL19_CRYNJ, Q5KC42_CRYNJ, Q5KNI6_CRYNJ, Q5KCS1_CRYNJ, Q5KNH2_CRYNJ, Q5KA46_CRYNJ, Q5KEV1_CRYNJ, Q5KFT0_CRYNJ, Q5KAB9_CRYNJ, Q5KN73_CRYNJ, Q5KLJ6_CRYNJ, and Q5KHQ2_CRYNJ, were selected for FDA-approved drugs screening using GNINA, resulting in three potential drugs (amphotericin B, idarubicin, and candicidin) for respective proteins.

The Ck2 complex in C. neoformans regulates cellular processes, including proliferation and apoptosis. Disruption of this complex affects cellular functions. This study identifies deletion mutations and pathogenic proteins, revealing top-performing drugs. Further clinical investigations are needed to confirm these findings.

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