Identification Of Transcriptional Regulators Involved In Azole Resistance In The Pathogenic Fungus Aspergillus fumigatus

Ref ID: 18455

Author:

Marcin Fraczek, Jane Gilsenan, Helena O’Flynn, Paul Bowyer, Michael Bromley

Author address:

University of Manchester

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Aspergillus fumigatus is an opportunistic human pathogen responsible for invasive and chronic disease. Treatment
of fungal infections is becoming increasingly difficult due to the emergence of resistance particularly to the azole
drug class. The key causes of clinical azole resistance are point mutations in the drug target (CYP51) however
isolates with non8208;target resistance mechanisms are being frequently isolated in our patient population. In an
attempt to identify some of these novel mechanisms we are exploring the role of transcription factors in
itraconazole reistance.
Availability of the complete genome sequence of A. fumigatus has enabled us to identify 450 transcription factors.
To enable disruption of all 450 of these genes we have devised a systematic approach to gene knockout coupling a
28208;step PCR fusion approach to a 968208;well transformation method. Our process, from the automated design of gene
KO primers to generation of KO cassettes strains and subsequent isolation of mutant isolates takes less than one
week per 96 strains. Several of the transcription factors we have identified appear to be critical to the viability of A.
fumigatus whilst many other mutants exhibit a range of gross phenotypic effects. We are currently analysing our
collection of gene deletion mutants to identify those transcription factors which are either resistant or sensitive to
azoles and other antifungal agents.

Abstract Number: PR1.36

Conference Year: 2012

Link to conference website: http://www.ecfg.info/images/Abstract_Book_Electronic.pdf

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