Differential Gene Expression Analysis in Candida albicans: A Comparative Study Between Malic Acid and Glucose Media for Insights into Pathogenicity and Metabolic Pathway Interactions

Candida albicans is a pathogenic fungus known for causing various human infections, ranging from localized candidiasis to systemic invasive conditions. This research examined variations in gene expression patterns of C. albicans when cultivated in malic acid and glucose media. Data set GSE223317 was extracted from the Gene Expression Omnibus (GEO) database. Bioinformatic analyses were executed using RStudio, utilizing the limma and edgeR packages. Following the normalization of the raw data, 278 differentially expressed genes (DEGs) were found, with 127 displaying increased expression and 151 demonstrating reduced expression in the malic acid medium compared to the glucose medium.
Subsequent analyses, including Gene Ontology (GO) and KEGG pathway mapping, were conducted via the Candida Genome Database and DAVID. These assessments unveiled substantial enrichment in biochemical pathways, including the Tricarboxylic Acid (TCA) Cycle and the biosynthesis of secondary metabolites. Furthermore, protein-protein connectivity networks were constructed with the assistance of the STRING database. Furthermore, hub genes associated with metabolic pathways relevant to the shift from glucose to malic acid as a carbon source were explored, utilizing protein-protein interaction analyses via the MCODE module and Cytohubba plugin in Cytoscape. The findings strongly indicate that transitioning from glucose to malic acid as a carbon source could enhance the metabolic adaptability and potential pathogenicity of C. albicans. Functional enrichment analyses also showed that key hub genes and top-ranking DEGs were significantly involved in oxidoreductase activity, mitochondrial function, and hyphal formation.
This work lays the groundwork for future research into how environmental factors, such as the type of carbon source, influence this opportunistic fungal pathogen's pathogenesis and drug resistance. Furthermore, the results suggested that switching from glucose to malic acid could modulate the pathogenicity and invasiveness of C. albicans, thereby enhancing our understanding of its colonization mechanisms in human organs.