2026-04-17T02:26:40Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/431212025-12-12T04:17:12Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Stefanini, Irene author Rizzetto, Lisa author Rivero, Damariz author Carbonell, Silvia author Gut, Marta author Heath, Simon author Gut, Ivo Glynne author Trabocchi, Andrea author Guarna, Antonio author Ben Ghazzi, Nagwa author Bowyer, Paul author Kapushesky, Misha author Cavalieri, Duccio author 2019-12-09T09:23:14Z 2019-12-09T09:23:14Z 2018 Fungal 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. This project was supported by European Union’s Seventh Framework Programme [FP7/2007-2013] under grant agreement n° HEALTH-2010-242220 (“SYBARIS”) and by EU Framework Programme 7 Collaborative Project [242220]-JPI ENPADASI. I.S. was supported by the “Sybaris” project and by a fellowship from the Wellcome Warwick Quantitative Biomedicine Programme (Institutional Strategic Support Fund: 105627/Z/14/Z). The authors would like to thank Enrica Calura and Gavin Sherlock for support and critical comments on the analyses. Antifungal agents Mechanism of action Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle