Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol

The inoculum size effect in the dimorphic fungus Candida albicans results f rom production of an extracellular quorum-sensing molecule (QSM). This mole cule prevents mycelial development in both a growth morphology assay and a differentiation assay using three chemically distinct triggers for germ tub e formation (GTF): L-proline, N-acetylglucosamine, and serum (either pig or fetal bovine). In all cases, the presence of QSM prevents the yeast-to-myc elium conversion, resulting in actively budding yeasts without influencing cellular growth rates. QSM exhibits general cross-reactivity within C, albi cans in that supernatants from strain A72 are active on five other strains of C, albicans and vice versa, The QSM excreted by C, albicans is farnesol (C15H26O; molecular weight, 222,37), QSM is extracellular, and is produced continuously during growth and over a temperature range from 23 to 43 degre esC, in amounts roughly proportional to the CFU/milliliter, Production is n ot dependent on the type of carbon source nor nitrogen source or on the che mical nature of the growth medium, Both commercial mixed isomer and (E,E)-f arnesol exhibited QSM activity (the ability to prevent GTF at a level suffi cient to account for all the QSM activity present in C, albicans supernatan ts, i.e., 50% GTF at ca, 30 to 35 muM. Nerolidol was ca, two times less act ive than farnesol, Neither geraniol (C-10), geranylgeraniol (C-20), nor far nesyl pyrophosphate had any QSM activity.