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

TitleDeciphering the mechanism of action of 089, a compound impairing the fungal cell cycle.
Publication TypeJournal Article
Year of Publication2018
AuthorsStefanini, 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
JournalSci Rep
Volume8
Issue1
Pagination5964
Date Published2018 Apr 13
ISSN2045-2322
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.

DOI10.1038/s41598-018-24341-y
Alternate JournalSci Rep
PubMed ID29654251
PubMed Central IDPMC5899093