A functional link between hyphal maintenance and quorum sensing in Candida albicans.
Morphogenesis in Candida albicans requires hyphal initiation and maintenance, and both processes are regulated by the fungal quorum sensing molecule (QSM) farnesol. We show that deletion of C. albicans EED1, which is crucial for hyphal extension and maintenance, led to a dramatically increased sensitivity to farnesol, and thus identified the first mutant hypersensitive to farnesol. Furthermore, farnesol decreased the transient filamentation of an eed1Δ strain without inducing cell death, indicating that two separate mechanisms mediate quorum sensing and cell lysis by farnesol. To analyze the cause of farnesol hypersensitivity we constructed either hyperactive or deletion mutants of factors involved in farnesol signaling, by introducing the hyperactive RAS1G13Vor pADH1-CYR1CATallele, or deleting CZF1 or NRG1 respectively. Neither of the constructs nor the exogenous addition of dB-cAMP was able to rescue the farnesol hypersensitivity, highlighting that farnesol mediates its effects not only via the cAMP pathway. Interestingly, the eed1Δ strain also displayed increased farnesol production. When eed1Δ was grown under continuous medium flow conditions, to remove accumulating QSMs from the supernatant, maintenance of eed1Δ filamentation, although not restored, was significantly prolonged, indicating a link between farnesol sensitivity, production, and the hyphal maintenance-defect in the eed1Δ mutant strain.
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.
Melanie
M
Polke
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.
Marcel
M
Sprenger
Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.
Kirstin
K
Scherlach
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.
María Cristina
MC
Albán-Proaño
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.
Ronny
R
Martin
Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.|Friedrich Schiller University, Jena, Germany.
Christian
C
Hertweck
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.|Friedrich Schiller University, Jena, Germany.|Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, Jena, Germany.
Bernhard
B
Hube
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute (HKI), Jena, Germany.|Friedrich Schiller University, Jena, Germany.|Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, Jena, Germany.
Ilse D
0000-0002-6033-9984
ID
Jacobsen
D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005204:Farnesol / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000254:growth & development* / Q000378:metabolism; D053038:Quorum Sensing / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D005656:Fungal Proteins; D014157:Transcription Factors; D037521:Virulence Factors; C077336:CZF1 protein, Candida albicans; D005204:Farnesol; D000242:Cyclic AMP