The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans

Rebecca A. Hall, Kara J. Turner, James Chaloupka, Fabien Cottier, Luisa De Sordi, Dominique Sanglard, Lonny R. Levin, Jochen Buck, Fritz A. Muehlschlegel

Research output: Contribution to journalArticle

80 Citations (Scopus)

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.
Original languageEnglish
Article numberPMC3165441
Pages (from-to)1034-1042
Number of pages9
JournalEukaryotic Cell
Volume10
Issue number8
Early online date10 Jun 2011
DOIs
Publication statusPublished - Aug 2011

Keywords

  • quorum sensing

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    Hall, R. A., Turner, K. J., Chaloupka, J., Cottier, F., De Sordi, L., Sanglard, D., Levin, L. R., Buck, J., & Muehlschlegel, F. A. (2011). The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans. Eukaryotic Cell, 10(8), 1034-1042. [PMC3165441]. https://doi.org/10.1128/EC.05060-11