Projects per year
The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.
|Publication status||Published - 22 Jan 2020|
FingerprintDive into the research topics of 'The Negative Cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus'. Together they form a unique fingerprint.
MFIG: Manchester Fungal Infection Group (MFIG)
Bromley, M., Bertuzzi, M., Gago, S., Denning, D., Kosmidis, C., Bowyer, P., Amich Elias, J., Richardson, M. & Richardson, R.
15/08/13 → …
Development of New Experimental Models to Understand the Genetic Basis of Allergic Bronchopulmonary Aaspergillosis (ABPA).
12/01/17 → 12/04/19