2026/02/08 by Dhara Malavia-Jones, Ian Leaves, Jemima Onime +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Antifungal resistance and susceptibility #Biochemical and Molecular Research #Fungal and yeast genetics research
paper · doi:10.1016/j.tcsw.2026.100170
openalex publication_date 2026/02/08 · openalex created_date 2026/02/10 · openalex updated_date 2026/07/23
Candida albicans is an opportunistic fungal pathogen that can cause a variety of superficial and life-threatening systemic infections. Relatively few clinically effective antifungal therapies are available, and the increasing prevalence of antifungal drug resistance poses a serious threat in treating these infections. Target validation of biochemical pathways that are essential for fungal growth offers an approach towards the design of novel antifungal drugs that address the growing requirement for new antifungal therapies. Therefore, we used the GRACE library of conditional mutants of C. albicans to explore enzymes in the sugar nucleotide biosynthesis pathway as potential drug targets. This pathway provides UDP- N -acetylglucosamine (UDP-GlcNAc), UDP-glucose (UDP-Glc) and GDP-mannose (GDP-Man) substrates for the synthesis of the essential cell wall polymers, chitin, β-glucan(s) and mannan(s). We show that the genes encoding GDP-mannose pyrophosphorylase ( SRB1/PSA1/VIG9 ), UTP-glucose-1-phosphaturidyl transferase ( UGP1 ), phosphoglucose isomerase ( PGI1 ) and glucosamine-6-phosphate synthase ( GFA1 ) are critical for growth, biofilm formation and virulence in C. albicans . Genes encoding other enzymes in the sugar nucleotide biosynthetic pathway (namely AGM1 , PMM1 , PMI1 , GNA1 and UAP1 ) were not essential for growth but were required for biofilm formation, tissue invasion and virulence. Repression of genes that encode these enzymes also resulted in hypersensitivity to a range of antifungal drugs as well as oxidative and cell wall stressors. These data underline the potential for augmenting antifungal drug development by targeting these enzymes in the treatment of C. albicans infections. • GDP-mannose pyrophosphorylase ( SRB1 ), UTP-glucose-1-phosphaturidyl transferase ( UGP1 ), phosphoglucose isomerase ( PGI1 ) and glucosamine-6-phosphate synthase ( GFA1 ) are required for the biosynthesis of sugar nucleotide substrates essential for construction of the fungal cell wall. • These enzymes are essential for the growth and virulence of C. albicans, but suppressing growth by repressing genes on the sugar nucleotide pathway did not always correlate with the loss of virulence associated traits. • Decreased SRB1 , UGP1 , PGI1 and GFA1 gene expression resulted in hypersensitivity to a range of antifungal drugs and cell wall stressors.