Identification of genes regulating cell wall permeability and antifungal responses in Aspergillus fumigatus

Ref ID: 19525

Author:

S Raj1*, R Beau1, M Fraczek2, JP Latgé1, M Bromley2

Author address:

1Unite des Aspergillus, Institut Pasteur, Paris, France
2Respiratory Research Medicine Group, University of Manchester, Manchester, United Kingdom

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Identification of novel antifungal drug targets is critical due to the increased incidences of systemic
fungal infections in the immunocompromised populations. Studies in Candida albicans have
attempted to identify novel transcription factors that may be associated with regulating antifungal
drug tolerance. With a library of mutants composed of systematic deletions in ca 350 transcription
factors, we decided to investigate novel global regulators of cell wall permeability and antifungal
responses in Aspergillus fumigatus.
Methods:
We began our studies by screening for mutants that exhibit increased resistance or sensitivity to cell
wall binding agents congo red (CR) and calcofluor white (CFW). These agents disrupt cell wall
assembly by binding to nascent chitin chains, thereby interrupting cross-linking with beta-glucan
polymers leading to a weakened cell wall.
Results:
Presently, we have identified five mutants which show resistance to both CR (300 μg/ml) and CFW
(150 μg/ml) and one specifically to CR. Amongst these, two were mutants in C2H2 zinc finger
transcription factors, one RNA polymerase II elongin subunit A and three C6 transcription factors.
One C2H2 mutant is the previously characterized CrzA-encoding transcription factor, demonstrated
to be involved in morphology and pathogenesis of A. fumigatus. Conversely, 22 mutants exhibited
increased sensitivity to CR (50 μg/ml) and six mutants to both CR and CFW (40 μg/ml). The majority
belonged to the C6 family (ten) while the rest spanned C2H2, bZIP, and GATA amongst others.
Conclusions:
Future work will involve RNA-sequence analyses on these mutants, to glean information on the
genes involved in/ associated with modification of cell wall permeability.

Abstract Number: 52

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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