Fungal echinocandin resistance

Louise A. Walker; Neil A. R. Gow; Carol A. Munro

doi:10.1016/j.fgb.2009.09.003

Fungal echinocandin resistance

Louise A. Walker, Neil A. R. Gow, Carol A. Munro

Medical Sciences

Research output: Contribution to journal › Literature review › peer-review

220 Citations (Scopus)

Abstract

The echinocandins are the newest class of antifungal agents in the clinical armory. These secondary metabolites are non-competitive inhibitors of the synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell wall. Recent work has shown that spontaneous mutations can arise in two hot spot regions of Fks1 the target protein of echinocandins that reduce the enzyme's sensitivity to the drug. However, other strains have been isolated in which the sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to echinocandins. In addition it has been shown that echinocandin-treatment can induce cell wall salvage mechanisms that result in the compensatory upregulation of chitin synthesis in the cell wall. This salvage mechanism strengthens cell walls damaged by exposure to echinocandins. Therefore, fungal resistance to echinocandins can arise due to the selection of either stable mutational or reversible physiological alterations that decrease susceptibility to these antifungal agents.

Original language	English
Pages (from-to)	117-126
Number of pages	10
Journal	Fungal Genetics and Biology
Volume	47
Issue number	2
Early online date	19 Sept 2009
DOIs	https://doi.org/10.1016/j.fgb.2009.09.003
Publication status	Published - Feb 2010

Bibliographical note

A paid open access option is available for this journal.
Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers
Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository
Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists
Set statement to accompany deposit
Published source must be acknowledged
Must link to journal home page or articles' DOI
Publisher's version/PDF cannot be used
Articles in some journals can be made Open Access on payment of additional charge
NIH Authors articles will be submitted to PubMed Central after <num>12</num> <period units="month">months</period>
Authors who are required to deposit in subject-based repositories may also use Sponsorship Option

Keywords

Antifungal Agents
Aspergillus fumigatus
Biofilms
Candida albicans
Cell Wall
Drug Resistance, Fungal
Echinocandins
Genome, Fungal
Humans
Models, Biological
Mycoses
Antifungals
Fungal cell wall
Glucan
Chitin

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title = "Fungal echinocandin resistance",

abstract = "The echinocandins are the newest class of antifungal agents in the clinical armory. These secondary metabolites are non-competitive inhibitors of the synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell wall. Recent work has shown that spontaneous mutations can arise in two hot spot regions of Fks1 the target protein of echinocandins that reduce the enzyme's sensitivity to the drug. However, other strains have been isolated in which the sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to echinocandins. In addition it has been shown that echinocandin-treatment can induce cell wall salvage mechanisms that result in the compensatory upregulation of chitin synthesis in the cell wall. This salvage mechanism strengthens cell walls damaged by exposure to echinocandins. Therefore, fungal resistance to echinocandins can arise due to the selection of either stable mutational or reversible physiological alterations that decrease susceptibility to these antifungal agents.",

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note = "A paid open access option is available for this journal. Voluntary deposit by author of pre-print allowed on Institutions open scholarly website and pre-print servers Voluntary deposit by author of authors post-print allowed on institutions open scholarly website including Institutional Repository Deposit due to Funding Body, Institutional and Governmental mandate only allowed where separate agreement between repository and publisher exists Set statement to accompany deposit Published source must be acknowledged Must link to journal home page or articles' DOI Publisher's version/PDF cannot be used Articles in some journals can be made Open Access on payment of additional charge NIH Authors articles will be submitted to PubMed Central after <num>12</num> <period units={"}month{"}>months</period> Authors who are required to deposit in subject-based repositories may also use Sponsorship Option",

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AU - Munro, Carol A.

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N2 - The echinocandins are the newest class of antifungal agents in the clinical armory. These secondary metabolites are non-competitive inhibitors of the synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell wall. Recent work has shown that spontaneous mutations can arise in two hot spot regions of Fks1 the target protein of echinocandins that reduce the enzyme's sensitivity to the drug. However, other strains have been isolated in which the sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to echinocandins. In addition it has been shown that echinocandin-treatment can induce cell wall salvage mechanisms that result in the compensatory upregulation of chitin synthesis in the cell wall. This salvage mechanism strengthens cell walls damaged by exposure to echinocandins. Therefore, fungal resistance to echinocandins can arise due to the selection of either stable mutational or reversible physiological alterations that decrease susceptibility to these antifungal agents.

AB - The echinocandins are the newest class of antifungal agents in the clinical armory. These secondary metabolites are non-competitive inhibitors of the synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell wall. Recent work has shown that spontaneous mutations can arise in two hot spot regions of Fks1 the target protein of echinocandins that reduce the enzyme's sensitivity to the drug. However, other strains have been isolated in which the sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to echinocandins. In addition it has been shown that echinocandin-treatment can induce cell wall salvage mechanisms that result in the compensatory upregulation of chitin synthesis in the cell wall. This salvage mechanism strengthens cell walls damaged by exposure to echinocandins. Therefore, fungal resistance to echinocandins can arise due to the selection of either stable mutational or reversible physiological alterations that decrease susceptibility to these antifungal agents.

KW - Antifungal Agents

KW - Aspergillus fumigatus

KW - Biofilms

KW - Candida albicans

KW - Cell Wall

KW - Drug Resistance, Fungal

KW - Echinocandins

KW - Genome, Fungal

KW - Humans

KW - Models, Biological

KW - Mycoses

KW - Antifungals

KW - Fungal cell wall

KW - Glucan

KW - Chitin

U2 - 10.1016/j.fgb.2009.09.003

DO - 10.1016/j.fgb.2009.09.003

M3 - Literature review

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SN - 1087-1845

VL - 47

SP - 117

EP - 126

JO - Fungal Genetics and Biology

JF - Fungal Genetics and Biology

IS - 2

ER -

Fungal echinocandin resistance

Abstract

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Keywords

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