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Poacic acid, a β‐1,3‐glucan–binding antifungal agent, inhibits cell‐wall remodeling and activates transcriptional responses regulated by the cell‐wall integrity and high‐osmolarity glycerol pathways in yeast
Author(s) -
García Raúl,
IttoNakama Kaori,
RodríguezPeña José Manuel,
Chen Xiaolin,
Sanz Ana Belén,
Lorenzo Alba,
PavónVergés Mónica,
Kubo Karen,
Ohnuki Shinsuke,
Nombela César,
Popolo Laura,
Ohya Yoshikazu,
Arroyo Javier
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100278r
Subject(s) - glucan , saccharomyces cerevisiae , biochemistry , yeast , echinocandins , cell wall , mode of action , biology , chemistry , microbiology and biotechnology , caspofungin , antifungal , amphotericin b
As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits β‐1,3‐glucan synthesis in Saccharomyces cerevisiae and has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to β‐1,3‐glucan, its affinity for which is ~30‐fold that for chitin. Besides its effect on β‐1,3‐glucan synthase activity, PA inhibited the yeast glucan‐elongating activity of Gas1 and Gas2 and the chitin–glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co‐regulation was mediated by parallel activation of the cell‐wall integrity (CWI) and high‐osmolarity glycerol signaling pathways. Despite targeting β‐1,3‐glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.