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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 ISSN 2045-2322.
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WRAP-deciphering-mechanism-action-089-compound-impairing-fungal-cell-cycle-Stefanini-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2552Kb) | Preview |
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 Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > 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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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 (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 3 May 2018 | ||||||||||||
Date of first compliant Open Access: | 4 May 2018 | ||||||||||||
RIOXX Funder/Project Grant: |
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