Virulence-associated genome plasticity of selected clinical candida albicans from a Philippine tertiary hospital

• Main Author: Gerodias, Maria Angelica R.
• Format: text
• Language: English
• Published: Animo Repository 2023
• Subjects: Candida albicans > Philippines; Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdb_bio/29
• Institution: De La Salle University

As an opportunistic fungus known to cause systemic infections in immunocompromised individuals, the genome of Candida albicans has been widely studied due to its high degree of genome plasticity which relates to resistance to antifungal agents such as azoles. It is therefore vital to elucidate possible changes in the genomes of clinical isolates which may have conferred greater virulence and resistance to antifungals. This study presented the assembled and functionally annotated genomes of azole-resistant and non-azole resistant clinical C. albicans isolates from a Philippine tertiary hospital. Paired-end reads obtained through Illumina sequencing were subjected to reference-guided assembly using available bioinformatics pipeline. Gene prediction and assessment of the genomes were performed using AUGUSTUS and BUSCO. The study was able to assemble 72.6% and 96.8% completeness for the non-azole resistant isolates, and 96.6% completeness for the azole-resistant isolates. The coding regions of the genomes were functionally annotated using Blast2GO to determine Gene Ontology (GO) Slim terms which describe the overall activity of the genes based on biological process, molecular function, and cellular component. This resulted in 88.6% and 85.5% annotation of the non-azole resistant isolates and 89.5% and 88.2% annotation of the azole-resistant isolates. Meanwhile, KEGG Automatic Annotation Server (KAAS) was utilized to determine KEGG Orthology (KO) assignments which groups genes acting on similar biological processes into pathways. Among the pathways detected in the clinical isolates were those that have previously been associated with pathogenesis, such as carbon metabolism (pentose phosphate pathway, glyoxylate cycle, glycolysis, gluconeogenesis), vitamin and cofactor biosynthesis (riboflavin, pantothenate, pyridoxal phosphate, and ubiquinone biosynthetic pathways), lipid metabolism (phosphatidylcholine and phosphatidylethanolamine biosynthesis, ceramide biosynthesis), and amino acid biosynthesis (shikimate pathway; threonine, isoleucine/valine, and arginine biosynthesis). Concurrently, the assembled genomes were also assessed for secondary metabolite gene clusters through fungiSMASH, which revealed the presence of l-aminoadipate-semialdehyde dehydrogenase and squalene synthase. Meanwhile, uncharacterized protein-coding sequences and mutations in the core biosynthetic genes were also detected, suggesting further investigation and characterization. Collectively, the study contributes to the knowledge about azole-resistant and non-azole resistant C. albicans and provides insight into its genomic diversity.