Plant-derived antifungal agent poacic acid targets β-1,3-glucan

Jeff S. Piotrowski, Hiroki Okada, Fachuang Lu, Sheena C. Li, Li Hinchman, Ashish Ranjan, Damon L. Smith, Alan J. Higbee, Arne Ulbrich, Joshua J. Coon, Raamesh Deshpande, Yury V. Bukhman, Sean McIlwain, Irene M. Ong, Chad L. Myers, Charles Boonec, Robert Landicka, John Ralpha, Mehdi Kabbaged, Yoshikazu Ohyab

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani aswell as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broadrange fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.

Original languageEnglish (US)
Pages (from-to)E1490-E1497
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number12
DOIs
StatePublished - Mar 24 2015

Bibliographical note

Publisher Copyright:
© 2015, National Academy of Sciences. All rights reserved.

Keywords

  • Chemical genomics
  • Fungal cell wall
  • High-dimensional morphometrics
  • Lignocellulosic hydrolysates
  • Saccharomyces cerevisiae

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