Narrow mutational signatures drive acquisition of multidrug resistance in the fungal pathogen Candida glabrata.

Anidulafungin / pharmacology Antifungal Agents / pharmacology Candida glabrata / genetics Drug Resistance, Fungal / genetics Drug Resistance, Multiple Fluconazole / pharmacology Microbial Sensitivity Tests Mutation
Candida glabrata antifungal cross-resistance drug resistance experimental evolution multidrug resistance

Journal

Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782

Informations de publication

Date de publication:
06 12 2021
Historique:
received: 09 03 2021
revised: 20 07 2021
accepted: 29 09 2021
pubmed: 27 10 2021
medline: 9 4 2022
entrez: 26 10 2021
Statut: ppublish

Résumé

Fungal infections are a growing medical concern, in part due to increased resistance to one or multiple antifungal drugs. However, the evolutionary processes underpinning the acquisition of antifungal drug resistance are poorly understood. Here, we used experimental microevolution to study the adaptation of the yeast pathogen Candida glabrata to fluconazole and anidulafungin, two widely used antifungal drugs with different modes of action. Our results show widespread ability of rapid adaptation to one or both drugs. Resistance, including multidrug resistance, is often acquired at moderate fitness costs and mediated by mutations in a limited set of genes that are recurrently and specifically mutated in strains adapted to each of the drugs. Importantly, we uncover a dual role of ERG3 mutations in resistance to anidulafungin and cross-resistance to fluconazole in a subset of anidulafungin-adapted strains. Our results shed light on the mutational paths leading to resistance and cross-resistance to antifungal drugs.

Identifiants

DOI: 10.1016/j.cub.2021.09.084 PMID: 34699784 PMC: PMC8660101
pubmed: 34699784
pii: S0960-9822(21)01352-X
doi: 10.1016/j.cub.2021.09.084
pmc: PMC8660101
pii:
doi:

Substances chimiques

Antifungal Agents 0
Fluconazole 8VZV102JFY
Anidulafungin 9HLM53094I

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5314-5326.e10

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Ewa Ksiezopolska (E)

Barcelona Supercomputing Centre (BSC-CNS), Life Sciences Department, Jordi Girona 29, 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Mechanisms of Disease Program, The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.

Miquel Àngel Schikora-Tamarit (MÀ)

Barcelona Supercomputing Centre (BSC-CNS), Life Sciences Department, Jordi Girona 29, 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Mechanisms of Disease Program, The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.

Reinhard Beyer (R)

Institute of Microbial Genetics and Core Facility Bioactive Substances: Screening and Analysis, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Strasse 24, 3430 Tulln an der Donau, Austria.

Juan Carlos Nunez-Rodriguez (JC)

Barcelona Supercomputing Centre (BSC-CNS), Life Sciences Department, Jordi Girona 29, 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Mechanisms of Disease Program, The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.

Christoph Schüller (C)

Institute of Microbial Genetics and Core Facility Bioactive Substances: Screening and Analysis, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Strasse 24, 3430 Tulln an der Donau, Austria.

Toni Gabaldón (T)

Barcelona Supercomputing Centre (BSC-CNS), Life Sciences Department, Jordi Girona 29, 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Mechanisms of Disease Program, The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain. Electronic address: toni.gabaldon@bsc.es.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Peptides cycliques › Échinocandines › Anidulafungine › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antifongiques › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Candida › Candida glabrata › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance microbienne aux médicaments › Résistance des champignons aux médicaments › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Multirésistance aux médicaments › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Triazoles › Fluconazole › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › Narrow mutational signatures drive acquisition...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Narrow mutational signatures drive acquisition...