Abstract: The instant invention relates to filamentous fungal host cells producing and secreting a heterologous polypeptide of interest, said mutant host cell comprising and expressing a mutated ireA gene or a homologue thereof encoding a modified IreA polypeptide or a homologue thereof, said modified IreA polypeptide or homologue thereof comprising amino acid substitutions in 5 positions corresponding to positions 81 and 84 in the Aspergillus niger IreA amino acid sequence shown in SEQ ID NO:16, as well as methods of producing a polypeptide of interest in said cells and methods for constructing said cells.

Abstract: The instant invention relates to filamentous fungal host cells producing and secreting a heterologous polypeptide of interest, said mutant host cell comprising and expressing a mutated ireA gene or a homologue thereof encoding a modified IreA polypeptide or a homologue thereof, said modified IreA polypeptide or homologue thereof comprising amino acid substitutions in 5 positions corresponding to positions 81 and 84 in the Aspergillus niger IreA amino acid sequence shown in SEQ ID NO:16, as well as methods of producing a polypeptide of interest in said cells and methods for constructing said cells.

Abstract: The present invention concerns methods of treating fungal infections and methods of screening compounds for activity in treating fungal infections. Methods of the invention include using an active compound such as fludioxonil to treat a Cryptococcus neoformans infection. Also included are methods and pharmaceutical compositions useful for treating fungal infections using a Hog1 activator such as fludioxonil and a calcineurin inhibitor in combination.