RRC ID 56294
Author Umeyama T, Hayashi Y, Shimosaka H, Inukai T, Yamagoe S, Takatsuka S, Hoshino Y, Nagi M, Nakamura S, Kamei K, Ogawa K, Miyazaki Y.
Title CRISPR/Cas9 Genome Editing To Demonstrate the Contribution of Cyp51A Gly138Ser to Azole Resistance in Aspergillus fumigatus.
Journal Antimicrob Agents Chemother
Abstract A pan-azole-resistant Aspergillus fumigatus strain with the cyp51A mutations Gly138Ser and Asn248Lys was isolated from a patient receiving long-term voriconazole treatment. PCR fragments containing cyp51A with the mutations were introduced along with the Cas9 protein and single guide RNA into the azole-resistant/susceptible strains. Recombinant strains showed increased susceptibility via the replacement of Ser138 by glycine. Genetic recombination, which has been hampered thus far in clinical isolates, can now be achieved using CRISPR/Cas9 genome editing.
Volume 62(9)
Published 2018-9-1
DOI 10.1128/AAC.00894-18
PII AAC.00894-18
PMID 29914956
PMC PMC6125507
MeSH Aged Antifungal Agents / therapeutic use* Aspergillosis / drug therapy* Aspergillus fumigatus / drug effects* Aspergillus fumigatus / genetics* Aspergillus fumigatus / isolation & purification CRISPR-Cas Systems / genetics Cytochrome P-450 Enzyme System / genetics* Drug Resistance, Fungal / genetics* Fungal Proteins / genetics* Gene Editing / methods* Humans Male Voriconazole / therapeutic use*
IF 4.715
Times Cited 11
Pathogenic eukaryotic microorganisms