ABSTRACTLiving as a commensal,Candida albicansmust adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects onC. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted byPseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of theCandidaadenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving theC. albicanshyphal repressor, Sfl1p. Deletion ofSFL1did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing inC. albicansis mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that theBurkholderia cenocepaciadiffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules.
RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development
