Azole resistance among clinical Aspergillus fumigatus species complex isolates in Greece: first detection of TR46-mediated resistance and azole-resistant cryptic species
Abstract
Objectives: To assess the prevalence of antifungal resistance among clinical Aspergillus fumigatus species complex (SC) isolates in Greece, focusing on azole resistance and its underlying molecular mechanisms.
Methods: A total of 249 clinical A. fumigatus SC isolates were collected from geographically distinct centres across Greece. Antifungal susceptibility testing (AFST) was conducted according to EUCAST guidelines. Cryptic species and azole-resistant A. fumigatus (ARAf) isolates underwent confirmatory molecular identification. ARAf sensu stricto (SS) isolates were further analysed by CYP51A gene and promoter sequencing to detect resistance-associated mutations.
Results: Most isolates (246/249; 99%) were identified as A. fumigatus SS, while three isolates were molecularly identified as A. fumigatiaffinis, A. lentulus and A. pseudoviridinutans. Amphotericin B and echinocandins demonstrated good in vitro activity against A. fumigatus SS, whereas posaconazole was the most active azole in vitro. Cryptic species exhibited reduced susceptibility compared with A. fumigatus SS. Two isolates (1%; A. fumigatiaffinis and A. lentulus) were amphotericin B-resistant. Five isolates (2%) were ARAf, including all three cryptic species (from patients with chronic pulmonary aspergillosis; one pan-ARAf) and two A. fumigatus SS strains. One ARAf SS isolate (from a cystic fibrosis patient) was pan-ARAf and harboured the TR46/Y121F/T289A CYP51A mutation, while the second (from an ICU patient) displayed resistance to itraconazole, isavuconazole and posaconazole without detectable CYP51A mutations.
Conclusions: Although the clinical ARAf rate remains low in Greece, the first detection of pan-azole resistance associated with environmentally driven resistance mechanisms or cryptic species highlights the importance of surveillance, accurate species identification and routine AFST.
Related
- Genomic insights into azole resistance in Aspergillus fumigatus: findings from global and South African clinical isolates.
- Fungicidal effects of eight disinfectants against resistant Candidozyma auris (formerly Candida auris), Aspergillus fumigatus, and Trichophyton indotineae
- Azole-resistant Aspergillus fumigatus: poultry farms and schools as sentinels in Portugal
- Inflammatory and metabolic dysregulation in a murine model of COPD-like lung injury with acute Aspergillus fumigatus challenge
- Assessment of antibacterial and antioxidant potentials of Aspergillus fumigatus crude extract, the isolated endophyte from Centella asiatica (L.) urban supported by molecular docking
BibTeX
@article{siopi2026azole,
title = {{Azole resistance among clinical Aspergillus fumigatus species complex isolates in Greece: first detection of TR46-mediated resistance and azole-resistant cryptic species}},
author = {Maria Siopi and Margarita Vargiami and Maria-Ioanna Beredaki and Aristea Velegraki and Levantia Zachariadou and Emmanuel Roilides and Georgios Chamilos and Stavroula Antonopoulou and Lemonia Skoura and Ana Alastruey-Izquierdo and Spyros Pournaras and Joseph Meletiadis},
journal = {JAC-antimicrobial resistance},
year = {2026},
month = nov,
doi = {10.1093/jacamr/dlag238},
url = {https://europepmc.org/article/PMC/PMC13724261},
note = {CC BY},
}
RIS
TY - JOUR
TI - Azole resistance among clinical Aspergillus fumigatus species complex isolates in Greece: first detection of TR46-mediated resistance and azole-resistant cryptic species
AU - Maria Siopi
AU - Margarita Vargiami
AU - Maria-Ioanna Beredaki
AU - Aristea Velegraki
AU - Levantia Zachariadou
AU - Emmanuel Roilides
AU - Georgios Chamilos
AU - Stavroula Antonopoulou
AU - Lemonia Skoura
AU - Ana Alastruey-Izquierdo
AU - Spyros Pournaras
AU - Joseph Meletiadis
PY - 2026
DA - 2026/11/02
JO - JAC-antimicrobial resistance
DO - 10.1093/jacamr/dlag238
UR - https://europepmc.org/article/PMC/PMC13724261
AB - Objectives: To assess the prevalence of antifungal resistance among clinical Aspergillus fumigatus species complex (SC) isolates in Greece, focusing on azole resistance and its underlying molecular mechanisms. Methods: A total of 249 clinical A. fumigatus SC isolates were collected from geographically distinct centres across Greece. Antifungal susceptibility testing (AFST) was conducted according to EUCAST guidelines. Cryptic species and azole-resistant A. fumigatus (ARAf) isolates underwent confirmatory molecular identification. ARAf sensu stricto (SS) isolates were further analysed by CYP51A gene and promoter sequencing to detect resistance-associated mutations. Results: Most isolates (246/249; 99%) were identified as A. fumigatus SS, while three isolates were molecularly identified as A. fumigatiaffinis, A. lentulus and A. pseudoviridinutans. Amphotericin B and echinocandins demonstrated good in vitro activity against A. fumigatus SS, whereas posaconazole was the most active azole in vitro. Cryptic species exhibited reduced susceptibility compared with A. fumigatus SS. Two isolates (1%; A. fumigatiaffinis and A. lentulus) were amphotericin B-resistant. Five isolates (2%) were ARAf, including all three cryptic species (from patients with chronic pulmonary aspergillosis; one pan-ARAf) and two A. fumigatus SS strains. One ARAf SS isolate (from a cystic fibrosis patient) was pan-ARAf and harboured the TR46/Y121F/T289A CYP51A mutation, while the second (from an ICU patient) displayed resistance to itraconazole, isavuconazole and posaconazole without detectable CYP51A mutations. Conclusions: Although the clinical ARAf rate remains low in Greece, the first detection of pan-azole resistance associated with environmentally driven resistance mechanisms or cryptic species highlights the importance of surveillance, accurate species identification and routine AFST.
SN - 2632-1823
ER -