Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan
Azole resistance in <i>Aspergillus fumigatus</i> has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in <i>cyp51A</i>. The objective of this study was to test the antifungal susceptibilities of <i>A. fumigatus</i> i...
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MDPI AG
2022-08-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/9/908 |
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| author | Tsun-Hao Hsu Po-Yen Huang Yun-Chen Fan Pei-Lun Sun |
| author_facet | Tsun-Hao Hsu Po-Yen Huang Yun-Chen Fan Pei-Lun Sun |
| author_sort | Tsun-Hao Hsu |
| collection | DOAJ |
| description | Azole resistance in <i>Aspergillus fumigatus</i> has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in <i>cyp51A</i>. The objective of this study was to test the antifungal susceptibilities of <i>A. fumigatus</i> isolates from Chang Gung Memorial Hospital (CGMH), the largest tertiary referral hospital in Taiwan, and to investigate <i>cyp51A</i> mutations in azole-resistant strains. <i>A. fumigatus</i> isolates preserved in the Research Laboratory of Medical Mycology of CGMH from 2015 to 2021 were used. Antifungal susceptibility testing was performed using the YeastOne<sup>TM</sup> method. Isolates with high minimal inhibitory concentrations (MICs) against antifungals were further tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Mutations in the <i>cyp51A</i> in azole-resistant strains were detected by Sanger sequencing. The overall prevalence of azole-resistant isolates was 1.77% (two out of 113 isolates). The two azole-resistant strains had tandem repeats (TR) in the promoter region and mutations in the <i>cyp51A</i> gene (TR<sub>34</sub>/L98H and TR<sub>34</sub>/L98H/S297T/F495I). One strain showed intermediate susceptibility to voriconazole, and its Cyp51A protein had five amino acid substitutions (F46Y/M172V/N248T/D255E/E427K). TR<sub>34</sub>/L98H and TR<sub>34</sub>/L98H/S297T/F495I are the most prevalent <i>cyp51A</i> mutations in Taiwan, mediating azole resistance based on current publications and our results. YeastOne<sup>TM</sup> was validated as a rapid tool for the antifungal susceptibility test; however, further confirmation by CLSI should be considered when MIC values of voriconazole, posaconazole, and amphotericin B are close to the clinical breakpoints or ecological cutoff values. |
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| language | English |
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| spelling | doaj.art-3b4a1d97da7a4d3ca9d29139eccd493b2023-11-23T17:09:04ZengMDPI AGJournal of Fungi2309-608X2022-08-018990810.3390/jof8090908Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in TaiwanTsun-Hao Hsu0Po-Yen Huang1Yun-Chen Fan2Pei-Lun Sun3Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333423, TaiwanDivision of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333423, TaiwanResearch Laboratory of Medical Mycology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333423, TaiwanDepartment of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333423, TaiwanAzole resistance in <i>Aspergillus fumigatus</i> has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in <i>cyp51A</i>. The objective of this study was to test the antifungal susceptibilities of <i>A. fumigatus</i> isolates from Chang Gung Memorial Hospital (CGMH), the largest tertiary referral hospital in Taiwan, and to investigate <i>cyp51A</i> mutations in azole-resistant strains. <i>A. fumigatus</i> isolates preserved in the Research Laboratory of Medical Mycology of CGMH from 2015 to 2021 were used. Antifungal susceptibility testing was performed using the YeastOne<sup>TM</sup> method. Isolates with high minimal inhibitory concentrations (MICs) against antifungals were further tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Mutations in the <i>cyp51A</i> in azole-resistant strains were detected by Sanger sequencing. The overall prevalence of azole-resistant isolates was 1.77% (two out of 113 isolates). The two azole-resistant strains had tandem repeats (TR) in the promoter region and mutations in the <i>cyp51A</i> gene (TR<sub>34</sub>/L98H and TR<sub>34</sub>/L98H/S297T/F495I). One strain showed intermediate susceptibility to voriconazole, and its Cyp51A protein had five amino acid substitutions (F46Y/M172V/N248T/D255E/E427K). TR<sub>34</sub>/L98H and TR<sub>34</sub>/L98H/S297T/F495I are the most prevalent <i>cyp51A</i> mutations in Taiwan, mediating azole resistance based on current publications and our results. YeastOne<sup>TM</sup> was validated as a rapid tool for the antifungal susceptibility test; however, further confirmation by CLSI should be considered when MIC values of voriconazole, posaconazole, and amphotericin B are close to the clinical breakpoints or ecological cutoff values.https://www.mdpi.com/2309-608X/8/9/908<i>Aspergillus fumigatus</i>azole resistancesusceptibility<i>cyp51A</i>TR<sub>34</sub>/L98Hmutation |
| spellingShingle | Tsun-Hao Hsu Po-Yen Huang Yun-Chen Fan Pei-Lun Sun Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan Journal of Fungi <i>Aspergillus fumigatus</i> azole resistance susceptibility <i>cyp51A</i> TR<sub>34</sub>/L98H mutation |
| title | Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan |
| title_full | Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan |
| title_fullStr | Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan |
| title_full_unstemmed | Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan |
| title_short | Azole Resistance and <i>cyp51A</i> Mutation of <i>Aspergillus fumigatus</i> in a Tertiary Referral Hospital in Taiwan |
| title_sort | azole resistance and i cyp51a i mutation of i aspergillus fumigatus i in a tertiary referral hospital in taiwan |
| topic | <i>Aspergillus fumigatus</i> azole resistance susceptibility <i>cyp51A</i> TR<sub>34</sub>/L98H mutation |
| url | https://www.mdpi.com/2309-608X/8/9/908 |
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