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

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 as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range 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.

Inhibition of microbial biofuel production in drought-stressed switchgrass hydrolysate

“…Chemical genomic analysis of these hydrolysates was performed as described previously using a collection of ~3500 yeast deletion mutants [19, 36]. 200 µL cultures of the pooled collection of S. cerevisiae deletion mutants were grown anaerobically in the different versions of ACSH and ASGH, or yeast-rich medium (YPD, 20 g/L peptone, 10 g/L yeast extract, 20 g/L glucose), diluted 1:1 with sterile water, in triplicate for 48 h at 30 °C.…”

“…The barcode counts for each yeast deletion mutant in the hydrolysates were normalized against the synthetic hydrolysate control (SynH2.1) [16] in order to define sensitivity or resistance of individual strains (chemical genetic interaction score). The pattern of genetic interaction scores for all mutant strains represents the chemical genomic profile or “biological fingerprint” of a sample [19, 36]. The clustergram of the chemical genomic profiles was created in Cluster 3.0 [37], and visualized in Treeview (v1.1.6r4) [38].…”

Blad-Containing Oligomer Fungicidal Activity on Human Pathogenic Yeasts. From the Outside to the Inside of the Target Cell

“…However, some destabilization of the cell wall structure may occur, without any visual effect by fluorescent labeling, due to its β- N -acetyl- D -glucosaminidase activity, at the end of the chitin polymer. In fact, the absence of visual damages at the cell wall does not imply a fully operational and structured wall, as the same can be observed even with cell wall-targeting drugs (Piotrowski et al, 2015). This might explain why the cell wall remained visually intact with calcofluor white staining, while the cells were becoming metabolically inactive, or even dead.…”

“…Propidium iodide may also be used as an indicator of cell leakage, or cell permeability (Piotrowski et al, 2015). In any case, it was here demonstrated that BCO induces cell membrane damage in C. albicans , and this surely contributes to its inhibitory and/or lethal effect on cells.…”

Design, synthesis, antiviral bioactivity and three‐dimensional quantitative structure–activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety

“…and bran. According to the literature, ferulic acid and its derivatives demonstrate extensive biological effects, such as antiviral, antibacterial and antitumor activities . Meanwhile, the literature shows that ferulic acid ester derivative activities are superior to those of ferulic acid amide derivatives .…”