|Title||Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Stefanini, I, Rizzetto, L, Rivero, D, Carbonell, S, Gut, M, Heath, S, Gut, IG, Trabocchi, A, Guarna, A, Ben Ghazzi, N, Bowyer, P, Kapushesky, M, Cavalieri, D|
|Date Published||2018 Apr 13|
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.
|Alternate Journal||Sci Rep|
|PubMed Central ID||PMC5899093|