Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in <i>Candida albicans</i>

A series of synthetic molecules combining a geranyl backbone with a heterocyclic or oxime head group are quorum-sensing molecules that block the yeast to mycelium transition in the dimorphic fungus Candida albicans. A number of the analogs have an IC50 ≤ 10 μM, a level of potency essentially identical to the natural quorum sensing signal, the sesquiterpene farnesol. Two of the most potent analogs, neither toxic toward healthy mice, display remarkably different effects when co-administered with C. albicans. While neither offers protection from candidiasis, one analog mimics farnesol in acting as a virulence factor, whereas the other has no effect. The results offer the first example of highly potent synthetic fungal quorum-sensing molecules, and provide the first evidence for the ability to decouple quorum sensing and virulence. Graphical abstract A series of farnesol analogs are potent quorum-sensing molecules for the human pathogen Candida albicans. Two of the most potent analogs display very different effects in a mammalian model of systemic candidiasis.