RT Journal Article
T1 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
A1 García Sánchez, Raúl
A1 Itto‐Nakama, Kaori
A1 Rodríguez Peña, José Manuel
A1 Chen, Xiaolin
A1 Sanz Santamaría, Ana Belén
A1 Lorenzo, Alba de
A1 Pavón Vergés, Mónica
A1 Kubo, Karen
A1 Ohnuki, Shinsuke
A1 Nombela Cano, César
A1 Popolo, Laura
A1 Ohya, Yoshikazu
A1 Arroyo, Javier
AB 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.
PB Federation of American Society of Experimental Biology (FASEB)
SN 0892-6638
YR 2021
FD 2021-08-12
LK https://hdl.handle.net/20.500.14352/4712
UL https://hdl.handle.net/20.500.14352/4712
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2021)
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Centro de excelencia para Glycomics
NO FEDER
NO Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón
DS Docta Complutense
RD 10 abr 2025