Prevalence, mechanisms and genetic relatedness of the human pathogenic fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the environment of Taiwan
Summary Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole‐resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of a...
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Published in: | Environmental microbiology Vol. 20; no. 1; pp. 270 - 280 |
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Abstract | Summary
Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole‐resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus‐positive samples and isolates respectively. Most (29, 85.3%) azole‐resistant isolates harboured TR34/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild‐type isolates. Microsatellite genotyping revealed both the global spread of the TR34/L98H isolates and the occurrence of TR34/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. |
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AbstractList | Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates respectively. Most (29, 85.3%) azole-resistant isolates harboured TR
/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR
/L98H isolates and the occurrence of TR
/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates respectively. Most (29, 85.3%) azole-resistant isolates harboured TR34 /L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34 /L98H isolates and the occurrence of TR34 /L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole‐resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus ‐positive samples and isolates respectively. Most (29, 85.3%) azole‐resistant isolates harboured TR 34 /L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild‐type isolates. Microsatellite genotyping revealed both the global spread of the TR 34 /L98H isolates and the occurrence of TR 34 /L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF , two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. Summary Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole‐resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus‐positive samples and isolates respectively. Most (29, 85.3%) azole‐resistant isolates harboured TR34/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild‐type isolates. Microsatellite genotyping revealed both the global spread of the TR34/L98H isolates and the occurrence of TR34/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. |
Author | Chen, Yee‐Chun Hsu, Ching‐Shan Choi, Pui‐Ching Liu, Wei‐Lun Wang, Hsuan‐Chen Lin, Yong‐Hong Wu, Chi‐Jung Hsieh, Ming‐I Lo, Hsiu‐Jung Huang, Jui‐Chang Shih, Hsin‐I Chen, Yu‐Hsin |
Author_xml | – sequence: 1 givenname: Hsuan‐Chen surname: Wang fullname: Wang, Hsuan‐Chen organization: Division of Infectious Diseases, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes – sequence: 2 givenname: Jui‐Chang surname: Huang fullname: Huang, Jui‐Chang organization: Division of Crop Environment, Tainan District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan – sequence: 3 givenname: Yong‐Hong surname: Lin fullname: Lin, Yong‐Hong organization: Division of Crop Environment, Kaohsiung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan – sequence: 4 givenname: Yu‐Hsin surname: Chen fullname: Chen, Yu‐Hsin organization: Division of Crop Improvement, Taichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan – sequence: 5 givenname: Ming‐I surname: Hsieh fullname: Hsieh, Ming‐I organization: Division of Infectious Diseases, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes – sequence: 6 givenname: Pui‐Ching surname: Choi fullname: Choi, Pui‐Ching organization: Division of Infectious Diseases, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes – sequence: 7 givenname: Hsiu‐Jung surname: Lo fullname: Lo, Hsiu‐Jung organization: China Medical University – sequence: 8 givenname: Wei‐Lun surname: Liu fullname: Liu, Wei‐Lun organization: Fu Jen Catholic University – sequence: 9 givenname: Ching‐Shan surname: Hsu fullname: Hsu, Ching‐Shan organization: Chia Nan University of Pharmacy and Science – sequence: 10 givenname: Hsin‐I surname: Shih fullname: Shih, Hsin‐I organization: National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University – sequence: 11 givenname: Chi‐Jung surname: Wu fullname: Wu, Chi‐Jung email: wucj@nhri.org.tw organization: National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University – sequence: 12 givenname: Yee‐Chun surname: Chen fullname: Chen, Yee‐Chun organization: National Taiwan University Hospital and College of Medicine |
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Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the... Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and... Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and... |
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SubjectTerms | Agricultural management Air Microbiology Antifungal Agents - therapeutic use Aspergillosis - drug therapy Aspergillosis - epidemiology Aspergillosis - microbiology Aspergillus fumigatus Aspergillus fumigatus - drug effects Aspergillus fumigatus - genetics Aspergillus fumigatus - isolation & purification Azoles Azoles - therapeutic use Clinical isolates Cytochrome P-450 Enzyme System - genetics Drug Resistance, Fungal - genetics Efflux Fungal Proteins - genetics Fungi Fungicides Genes Genotype Genotypes Genotyping Growth rate Health risks Heterocyclic compounds Humans Itraconazole Itraconazole - therapeutic use Microbial Sensitivity Tests Microsatellite Repeats - genetics Microsatellites Municipalities Mutation Mutation - genetics Pesticides Posaconazole Prevalence Soil Soil Microbiology Surveillance Taiwan - epidemiology Triazoles - therapeutic use Voriconazole Voriconazole - therapeutic use Yard waste |
Title | Prevalence, mechanisms and genetic relatedness of the human pathogenic fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the environment of Taiwan |
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