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.

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, 8 (1): 5964. doi: 10.1038/s41598-018-24341-y handle: http://hdl.handle.net/10449/47685

Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle

Stefanini, I.
Primo
;
Rizzetto, L.;Cavalieri, D.
Ultimo
2018-01-01

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.
Settore BIO/19 - MICROBIOLOGIA GENERALE
2018
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, 8 (1): 5964. doi: 10.1038/s41598-018-24341-y handle: http://hdl.handle.net/10449/47685
File in questo prodotto:
File Dimensione Formato  
Stefanini et al 089 2018.pdf

accesso aperto

Licenza: Creative commons
Dimensione 2.21 MB
Formato Adobe PDF
2.21 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10449/47685
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact