Jessica J Talbot1, Shradha Subedi2,3, Catriona L Halliday2, David E Hibbs4, Felcia Lai4, Francisco J Lopez-Ruiz5, Lincoln Harper5, Robert F Park6, William S Cuddy7, Chayanika Biswas2,8, Louise Cooley9, Dee Carter8,10, Tania C Sorrell8, Vanessa R Barrs1,8, Sharon C-A Chen2,8. 1. Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, New South Wales, Australia. 2. Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, New South Wales Health Pathology, Westmead Hospital, The University of Sydney, Westmead, New South Wales, Australia. 3. Department of Infectious Diseases, Sunshine Coast University Hospital, Queensland, Australia. 4. Faculty of Pharmacy, The University of Sydney, New South Wales, Australia. 5. Centre for Crop and Disease Management, School of Molecular and Life Sciences, Curtin University, Bentley, Western Australia, Australia. 6. Judith & David Coffey Chair of Sustainable Agriculture, University of Sydney Plant Breeding Institute Cobbitty, The University of Sydney, New South Wales, Australia. 7. NSW Department of Primary Industries, co-located at the Elizabeth Macarthur Agricultural Institute, Menangle and the University of Sydney's Plant Breeding Institute Cobbitty, The University of Sydney, New South Wales, Australia. 8. The University of Sydney, Marie Bashir Institute for Infectious Diseases and Biosecurity and Westmead Clinical School and The Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Westmead, New South Wales, Australia. 9. Department of Microbiology and Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania, Australia. 10. School of Life and Environmental Sciences, The University of Sydney, New South Wales, Australia.
Abstract
Background: The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. Methods: A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Results: Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Conclusions: Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.
Background: The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. Methods:A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Results: Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Conclusions: Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.
Authors: A Arastehfar; A Carvalho; J Houbraken; L Lombardi; R Garcia-Rubio; J D Jenks; O Rivero-Menendez; R Aljohani; I D Jacobsen; J Berman; N Osherov; M T Hedayati; M Ilkit; D James-Armstrong; T Gabaldón; J Meletiadis; M Kostrzewa; W Pan; C Lass-Flörl; D S Perlin; M Hoenigl Journal: Stud Mycol Date: 2021-05-10 Impact factor: 16.097
Authors: Tra My N Duong; Phuong Tuyen Nguyen; Thanh Van Le; Huong Lan P Nguyen; Bich Ngoc T Nguyen; Bich Phuong T Nguyen; Thu Anh Nguyen; Sharon C-A Chen; Vanessa R Barrs; Catriona L Halliday; Tania C Sorrell; Jeremy N Day; Justin Beardsley Journal: J Fungi (Basel) Date: 2020-11-18