Functional and molecular characterization of Aspergillus fumigatus phosphoglucomutase (Pgm): a potential target for antifungal therapy

Introduction. Aspergillus fumigatus phosphoglucomutase ( Af PGM) is a central enzyme in fungal carbohydrate metabolism that catalyses the interconversion of glucose-1-phosphate and glucose-6-phosphate, generating precursors such as uridine diphosphate glucose required for the synthesis of key cell wall polysaccharides. Hypothesis/Gap Statement. Although Af PGM has been implicated in fungal viability and cell wall integrity, further functional and molecular characterization is required to better define its role in cell wall-associated processes and to evaluate its potential as a selective antifungal target. Aim. This study aimed to further characterize the functional contribution of Af PGM to fungal growth, cell wall-related phenotypes, biofilm formation and enzymatic activity. Methodology. A conditional A. fumigatus P alcA ::pgm mutant was used to assess growth, soluble β -glucan levels and biofilm formation. Functional complementation was evaluated by heterologous expression of Afpgm in a Saccharomyces cerevisiae pgm2Δ strain. Enzymatic inhibition was examined using the isothiazolone compound ISFP10. Results. Reduced Af PGM activity was associated with impaired growth, altered cell wall-related phenotypes, decreased soluble β -glucan levels and diminished biofilm biomass. Expression of Afpgm restored growth and sedimentation defects in the yeast pgm2Δ mutant to WT levels, confirming functional conservation. ISFP10 inhibited Af PGM activity and disrupted associated fungal phenotypes. Conclusion. These findings further define the functional role of Af PGM in fungal carbohydrate metabolism and cell wall-associated biology. The selective inhibition of Af PGM relative to human phosphoglucomutase supports its potential as a promising target for the development of novel antifungal therapies.