The Aspergillus nidulans alcA promoter drives tightly regulated conditional gene expression in Aspergillus fumigatus permitting validation of essential genes in this human pathogen

Abstract

Aspergillus fumigatus causes invasive aspergillosis, a mycosis that is usually fatal in immunocompromised patients. Functional genomics in this fungus will aid the discovery of novel antifungal drugs to treat invasive aspergillosis. However, there is still a need for appropriate molecular genetic tools to facilitate such functional studies. Here, we describe the use of a conditional gene expression system allowing the identification of novel therapeutic targets through validation of essential genes in A. fumigatus. This system is based on the capacity of the Aspergillus nidulans alcA promoter ( alcA p) to tightly regulate gene expression in this fungus. Conditionally regulated gene expression in A. fumigatus was demonstrated by transcriptional and phenotypic analyses of strains expressing a nuclear migration gene with a terminal phenotype, the A. fumigatus nudC gene, under control of this promoter. This conditional expression system, the first one described in A. fumigatus, will also be useful for investigating the function of essential genes by altering the threonine/glucose ratio in the growth medium.