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

Lookup NU author(s): Dr Joost Van Den Heuvel


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©2017 The Author(s) Published by the Royal Society. All rights reserved. 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.

Publication metadata

Author(s): Zhang J, Van Den Heuvel J, Debets AJM, Verweij PE, Melchers WJG, Zwaan BJ, Schoustra SE

Publication type: Article

Publication status: Published

Journal: Proceedings of the Royal Society B: Biological Sciences

Year: 2017

Volume: 284

Issue: 1863

Online publication date: 20/09/2017

Acceptance date: 22/08/2017

ISSN (print): 0962-8452

ISSN (electronic): 1471-2954

Publisher: Royal Society Publishing


DOI: 10.1098/rspb.2017.0635


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