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.

Autor: García R; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., Itto-Nakama K; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan., Rodríguez-Peña JM; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., Chen X; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan., Sanz AB; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., de Lorenzo A; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., Pavón-Vergés M; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., Kubo K; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan., Ohnuki S; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan., Nombela C; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain., Popolo L; Department of Biosciences, University of Milan, Milan, Italy., Ohya Y; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan.; Collaborative Research Institute for Innovative Microbiology (CRIIM), The University of Tokyo, Tokyo, Japan., Arroyo J; Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, Madrid, Spain.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Sep; Vol. 35 (9), pp. e21778.
DOI: 10.1096/fj.202100278R
Abstrakt: 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.
(© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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