A strain-specific role for the UDP-glucose 4-epimerase Uge3 in Aspergillus fumigatus virulence

How expression of hrmA contributes to virulence and worse disease progression is ill-defined. Surprisingly, increased hrmA expression results in loose attachment of the extracellular matrix (ECM) from the fungal cell wall resulting in decreased strain adherence.

Fungal strains that are less adherent in vitro are typically less virulent as the ECM aids in adhesion to host cells and confers protection from host responses. Here we report that the UDP-glucose 4-epimerase encoding gene, uge3, that is required for GAG biosynthesis is necessary for virulence of the H-MORPH strain, hrmAREV (AF293::hrmAD304G) in contrast to its parent strain AF293. We leverage an isogenic set of A. fumigatus strains to identify a role for uge3 in central carbon metabolism that promotes disease progression complementing its essential role in GAG biosynthesis in a strain specific context.