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

被引:11
作者
Garcia, Raul [1 ]
Itto-Nakama, Kaori [2 ]
Rodriguez-Pena, Jose Manuel [1 ]
Chen, Xiaolin [2 ]
Sanz, Ana Belen [1 ]
de Lorenzo, Alba [1 ]
Pavon-Verges, Monica [1 ]
Kubo, Karen [2 ]
Ohnuki, Shinsuke [2 ]
Nombela, Cesar [1 ]
Popolo, Laura [3 ]
Ohya, Yoshikazu [2 ,4 ]
Arroyo, Javier [1 ]
机构
[1] Univ Complutense Madrid, Fac Farm, Dept Microbiol & Parasitol, IRYCIS, Madrid 28040, Spain
[2] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Kashiwa, Chiba, Japan
[3] Univ Milan, Dept Biosci, Milan, Italy
[4] Univ Tokyo, Collaborat Res Inst Innovat Microbiol CRIIM, Tokyo, Japan
关键词
beta-1,3-glucan; antifungal agents; cell wall remodeling; MAPK; poacic acid; Saccharomyces cerevisiae; transcriptomics; transglycosylases; SACCHAROMYCES-CEREVISIAE; CATALYTIC-PROPERTIES; FLUORESCENCE ASSAY; MAPK PATHWAY; CHITIN; STRESS; EXPRESSION; MEMBRANE; DAMAGE; FAMILY;
D O I
10.1096/fj.202100278R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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 beta-1,3-glucan, its affinity for which is similar to 30-fold that for chitin. Besides its effect on beta-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 beta-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.
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页数:18
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