Stefanini, IreneRizzetto, LisaRivero, DamarizCarbonell, SilviaGut, MartaHeath, SimonGut, Ivo GlynneTrabocchi, AndreaGuarna, AntonioBen Ghazzi, NagwaBowyer, PaulKapushesky, MishaCavalieri, Duccio2019-12-092019-12-092018Stefanini I, Rizzetto L, Rivero D, Carbonell S, Gut M, Heath S et al. Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle. Sci Rep. 2018;8(1):5964. DOI: 10.1038/s41598-018-24341-y2045-2322http://hdl.handle.net/10230/43121Fungal infections represent an increasingly relevant clinical problem, primarily because of the increased survival of severely immune-compromised patients. Despite the availability of active and selective drugs and of well-established prophylaxis, classical antifungals are often ineffective as resistance is frequently observed. The quest for anti-fungal drugs with novel mechanisms of action is thus important. Here we show that a new compound, 089, acts by arresting fungal cells in the G2 phase of the cell cycle through targeting of SWE1, a mechanism of action unexploited by current anti-fungal drugs. The cell cycle impairment also induces a modification of fungal cell morphology which makes fungal cells recognizable by immune cells. This new class of molecules holds promise to be a valuable source of novel antifungals, allowing the clearance of pathogenic fungi by both direct killing of the fungus and enhancing the recognition of the pathogen by the host immune system.application/pdfeng© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-018-24341-yAntifungal agentsMechanism of actioninfo:eu-repo/semantics/openAccess