RRC ID 56261
Author Hagiwara D, Arai T, Takahashi H, Kusuya Y, Watanabe A, Kamei K.
Title Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG-CoA Reductase.
Journal Emerg Infect Dis
Abstract The recent increase in azole-resistant Aspergillus fumigatus is a global concern. Identifying the mutations that confer azole resistance is essential for developing novel methods for prompt diagnosis and effective drug treatment. We screened A. fumigatus clinical isolates for novel mutations conferring azole resistance. We compared the genomic sequences of susceptible and resistant isolates without mutations in cyp51A (non-cyp51A) and found mutations in hmg1 and erg6 involved in ergosterol biosynthesis. We also found the novel mutations in these genes in azole-resistant isolates with different genetic backgrounds. The resistant isolates with mutations in hmg1 showed increased intracellular ergosterol levels compared with susceptible isolates. This finding supports the concept that the ergosterol level is a determinant for resistance to any class of azoles. Multiple isolates with increased resistance to azole possessed a mutation in hmg1, indicating that this mutation is widely present in non-cyp51A azole-resistant A. fumigatus.
Volume 24(10)
Pages 1889-1897
Published 2018-10-1
DOI 10.3201/eid2410.180730
PMID 30226177
PMC PMC6154143
MeSH Aspergillosis / microbiology* Aspergillus fumigatus / drug effects* Aspergillus fumigatus / genetics* Aspergillus fumigatus / isolation & purification Aspergillus fumigatus / metabolism Azoles / pharmacology* Cytochrome P-450 Enzyme System / genetics* DNA, Fungal Drug Resistance, Fungal* Ergosterol / metabolism Fungal Proteins / genetics* Genes, Fungal Genome, Fungal Genotyping Techniques Humans Hydroxymethylglutaryl CoA Reductases / genetics* Microbial Sensitivity Tests Microsatellite Repeats Mutation* Polymorphism, Single Nucleotide
IF 7.185
Times Cited 9
Pathogenic eukaryotic microorganisms 病原真菌: IFM 60814, IFM 63240, IFM 63241, IFM 63242, IFM 63243. IFM 54229 (= Af293)