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Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle
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Stefanini, Irene, Rizzetto, Lisa, Rivero, Damariz, Carbonell, Silvia, Gut, Marta, Heath, Simon, Gut, Ivo G, Trabocchi, Andrea, Guarna, Antonio, Ben Ghazzi, Nagwa, Bowyer, Paul, Kapushesky, Misha and Cavalieri, Duccio (2018) Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle. Scientific Reports, 8 (1). 5964. doi:10.1038/s41598-018-24341-y
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Official URL: https://doi.org/10.1038/s41598-018-24341-y
Abstract
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.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Antifungal agents, Skin -- Infections -- Treatment | ||||||||||||
| Journal or Publication Title: | Scientific Reports | ||||||||||||
| Publisher: | Nature Publishing Group | ||||||||||||
| ISSN: | 2045-2322 | ||||||||||||
| Official Date: | 13 April 2018 | ||||||||||||
| Dates: |
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| Date of first compliant deposit: | 3 May 2018 | ||||||||||||
| Volume: | 8 | ||||||||||||
| Number: | 1 | ||||||||||||
| Article Number: | 5964 | ||||||||||||
| DOI: | 10.1038/s41598-018-24341-y | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||
| RIOXX Funder/Project Grant: |
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