Fungal echinocandin resistance

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

Research output: Contribution to journalLiterature review

146 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 languageEnglish
Pages (from-to)117-126
Number of pages10
JournalFungal Genetics and Biology
Volume47
Issue number2
Early online date19 Sep 2009
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Echinocandins
Cell Wall
Antifungal Agents
Fungal Structures
Chitin
Fungi
Up-Regulation
Mutation
Enzymes
Pharmaceutical Preparations

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

Cite this

Fungal echinocandin resistance. / Walker, Louise A.; Gow, Neil A. R.; Munro, Carol A.

In: Fungal Genetics and Biology, Vol. 47, No. 2, 02.2010, p. 117-126.

Research output: Contribution to journalLiterature review

Walker, Louise A. ; Gow, Neil A. R. ; Munro, Carol A. / Fungal echinocandin resistance. In: Fungal Genetics and Biology. 2010 ; Vol. 47, No. 2. pp. 117-126.
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