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
Main Authors: Wang, Hsuan‐Chen, Huang, Jui‐Chang, Lin, Yong‐Hong, Chen, Yu‐Hsin, Hsieh, Ming‐I, Choi, Pui‐Ching, Lo, Hsiu‐Jung, Liu, Wei‐Lun, Hsu, Ching‐Shan, Shih, Hsin‐I, Wu, Chi‐Jung, Chen, Yee‐Chun
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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.
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
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  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
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  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
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  givenname: Pui‐Ching
  surname: Choi
  fullname: Choi, Pui‐Ching
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  fullname: Liu, Wei‐Lun
  organization: Fu Jen Catholic University
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  surname: Hsu
  fullname: Hsu, Ching‐Shan
  organization: Chia Nan University of Pharmacy and Science
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  organization: National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University
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  givenname: Yee‐Chun
  surname: Chen
  fullname: Chen, Yee‐Chun
  organization: National Taiwan University Hospital and College of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29124846$$D View this record in MEDLINE/PubMed
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Snippet Summary 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
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2F1462-2920.13988
https://www.ncbi.nlm.nih.gov/pubmed/29124846
https://www.proquest.com/docview/1986293226
https://search.proquest.com/docview/1963275761
Volume 20
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