Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

Jianhua Zhang, Joost van den Heuvel, Fons Debets, Paul E. Verweij, Willem J.G. Melchers, Bas J. Zwaan, Sijmen E. Schoustra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.

Original languageEnglish
Article number20170635
JournalProceedings of the Royal Society. B: Biological Sciences
Volume284
Issue number1863
DOIs
Publication statusPublished - 2017

Fingerprint

Fungicides
triazoles
Triazoles
Aspergillus fumigatus
sterol
Aspergillus
cross resistance
fungicide
fungicides
Biosynthesis
Pressure
Sterols
sterols
biosynthesis
mutation
triazole fungicides
Genes
fungicide resistance
selection pressure
genome

Keywords

  • Aspergillus fumigatus
  • Evolutionary trajectory
  • Experimental evolution
  • Sterol-biosynthesis-inhibiting (SI) fungicides and medical triazoles
  • Triazole resistance

Cite this

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title = "Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides",
abstract = "Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.",
keywords = "Aspergillus fumigatus, Evolutionary trajectory, Experimental evolution, Sterol-biosynthesis-inhibiting (SI) fungicides and medical triazoles, Triazole resistance",
author = "Jianhua Zhang and {van den Heuvel}, Joost and Fons Debets and Verweij, {Paul E.} and Melchers, {Willem J.G.} and Zwaan, {Bas J.} and Schoustra, {Sijmen E.}",
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T1 - Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

AU - Zhang, Jianhua

AU - van den Heuvel, Joost

AU - Debets, Fons

AU - Verweij, Paul E.

AU - Melchers, Willem J.G.

AU - Zwaan, Bas J.

AU - Schoustra, Sijmen E.

PY - 2017

Y1 - 2017

N2 - Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.

AB - Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.

KW - Aspergillus fumigatus

KW - Evolutionary trajectory

KW - Experimental evolution

KW - Sterol-biosynthesis-inhibiting (SI) fungicides and medical triazoles

KW - Triazole resistance

U2 - 10.1098/rspb.2017.0635

DO - 10.1098/rspb.2017.0635

M3 - Article

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JO - Proceedings of the Royal Society. B: Biological Sciences

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