title: The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans.
abstract: Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. 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-C(12)-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl 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 the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C(12)-homoserine lactone, may be used by other quorum-sensing molecules.
authors.affiliation: School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom. F.A.Muhlschlegel@kent.ac.uk.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Hall
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Turner
authors.forename: James
authors.initials: J
authors.lastname: Chaloupka
authors.forename: Fabien
authors.initials: F
authors.lastname: Cottier
authors.forename: Luisa
authors.initials: L
authors.lastname: De Sordi
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.forename: Lonny R
authors.initials: LR
authors.lastname: Levin
authors.forename: Jochen
authors.initials: J
authors.lastname: Buck
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D007851:Dodecanol / Q000494:pharmacology*; D057075:Enzyme Assays; D005204:Farnesol / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D018384:Oxidative Stress; D053038:Quorum Sensing; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D005656:Fungal Proteins; D014157:Transcription Factors; C088386:homoserine lactone; D007851:Dodecanol; D005204:Farnesol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015107:4-Butyrolactone