Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle
Autor: | Andrea Trabocchi, Silvia Carbonell, Antonio Guarna, Duccio Cavalieri, Irene Stefanini, Marta Gut, Paul Bowyer, Damariz Rivero, Ivo Gut, Misha Kapushesky, Nagwa Ben Ghazzi, Lisa Rizzetto, Simon Heath |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
G2 Phase RM Antifungal Agents 030106 microbiology lcsh:Medicine Fungus Saccharomyces cerevisiae Mechanism of action Cell morphology Article RS Cell Line 03 medical and health sciences Immune system Cell Line Tumor medicine Animals Humans lcsh:Science Antifungal agents Pathogen Mammals Multidisciplinary Cell Cycle Fungi Mycoses biology lcsh:R Cell cycle biology.organism_classification 3. Good health Cell biology fungi phenotypic screening small molecules infectious diseases genomics cell morphology 030104 developmental biology Cell culture lcsh:Q medicine.symptom K562 Cells Settore BIO/19 - MICROBIOLOGIA GENERALE K562 cells |
Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) Scientific Reports Stefanini, I, Rizzetto, L, Rivero, D, Carbonell, S, Gut, M, Heath, S, Gut, I G, Trabocchi, A, Guarna, A, Ben Ghazzi, N, Bowyer, P, Kapushesky, M & Cavalieri, D 2018, ' Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle ', Scientific Reports, vol. 8, no. 1, 5964 . https://doi.org/10.1038/s41598-018-24341-y Recercat. Dipósit de la Recerca de Catalunya instname |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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