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

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 to...

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Bibliographic Details
Published in:Fungal genetics and biology 2003-11, Vol.40 (2), p.103-114
Main Authors: Romero, Beatriz, Turner, Geoffrey, Olivas, Israel, Laborda, Fernando, Ramón De Lucas, J
Format: Article
Language:English
Subjects:
alcA promoter
Alcohol Dehydrogenase - genetics
alcR gene
Aspergillus fumigatus
Aspergillus fumigatus - cytology
Aspergillus fumigatus - genetics
Aspergillus fumigatus - growth & development
Aspergillus fumigatus - metabolism
Aspergillus nidulans
Aspergillus nidulans - genetics
Blotting, Northern
Blotting, Southern
Cloning, Molecular
Conditional gene expression
DNA, Fungal - chemistry
DNA, Fungal - genetics
DNA, Fungal - isolation & purification
Essential genes
Functional analysis
Gene Expression Regulation, Fungal
Genes, Essential
Genes, Fungal
Invasive aspergillosis
Molecular genetic tools
Molecular Sequence Data
nudC gene
Promoter Regions, Genetic
Recombination, Genetic
RNA, Messenger - analysis
Threonine - metabolism
Transcription, Genetic
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Summary: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.
ISSN:1087-1845
1096-0937
DOI:10.1016/S1087-1845(03)00090-2