RRC ID 52832
Author Hagiwara D, Watanabe A, Kamei K.
Title Sensitisation of an Azole-Resistant Aspergillus fumigatus Strain containing the Cyp51A-Related Mutation by Deleting the SrbA Gene.
Journal Sci Rep
Abstract Azoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of cyp51A, and have disseminated globally in a short period of time. In this study, we investigated whether an azole-resistant strain with a 46-bp TR (TR46/Y121F/T289A) could be sensitised to azoles by deletion of srbA, encoding a direct regulator of cyp51A. The loss of SrbA did not affect colony growth or conidia production, but decreased expression of cyp51A. The srbA deletion strain showed hyper-susceptibility to medical azoles as well as azole fungicides, while its sensitivity to non-azole fungicides was unchanged. This is the first demonstration that deletion of a regulator of cyp51A can sensitise an azole-resistant A. fumigatus strain. This finding may assist in the development of new drugs to help combat life-threatening azole-resistant fungal pathogens.
Volume 6
Pages 38833
Published 2016-12-9
DOI 10.1038/srep38833
PII srep38833
PMID 27934927
PMC PMC5146965
MeSH Antifungal Agents / pharmacology* Aspergillus fumigatus / drug effects* Aspergillus fumigatus / genetics Azoles / pharmacology* Cytochrome P-450 Enzyme System / biosynthesis* Cytochrome P-450 Enzyme System / genetics Drug Resistance, Multiple, Fungal / genetics* Fungal Proteins / biosynthesis Fungal Proteins / genetics* Fungicides, Industrial / pharmacology* Gene Deletion Gene Expression Regulation, Fungal / genetics* Genes, Fungal* Mutation Oxygen / pharmacology Tandem Repeat Sequences Transcription Factors / genetics*
IF 3.998
Times Cited 9
Pathogenic microorganisms