The Transposon impala Is Activated by Low Temperatures: Use of a Controlled Transposition System To Identify Genes Critical for Viability of Aspergillus fumigatus

Author:

Carr Paul D.1,Tuckwell Danny1,Hey Peter M.1,Simon Laurence23,d'Enfert Christophe23,Birch Mike1,Oliver Jason D.1,Bromley Michael J.14

Affiliation:

1. F2G Limited, Lankro Way, Eccles, Manchester, United Kingdom;

2. Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Département Génomes et Génétique, F-75015 Paris, France; and

3. INRA USC2019, F-75015 Paris, France

4. The University of Manchester, Department of Translational Medicine, Manchester Academic Health Science Centre, Manchester, United Kingdom;

Abstract

ABSTRACT Genes that are essential for viability represent potential targets for the development of anti-infective agents. However, relatively few have been determined in the filamentous fungal pathogen Aspergillus fumigatus . A novel solution employing parasexual genetics coupled with transposon mutagenesis using the Fusarium oxysporum transposon impala had previously enabled the identification of 20 essential genes from A. fumigatus ; however, further use of this system required a better understanding of the mode of action of the transposon itself. Examination of a range of conditions indicated that impala is activated by prolonged exposure to low temperatures. This newly identified property was then harnessed to identify 96 loci that are critical for viability in A. fumigatus , including genes required for RNA metabolism, organelle organization, protein transport, ribosome biogenesis, and transcription, as well as a number of noncoding RNAs. A number of these genes represent potential targets for much-needed novel antifungal drugs.

Publisher

American Society for Microbiology

Subject

Molecular Biology,General Medicine,Microbiology

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