Previous Article | Next Article 
Applied and Environmental Microbiology, July 2001, p. 2982-2992, Vol. 67, No. 7
0099-2240/01/$04.00+0 DOI: 10.1128/AEM.67.7.2982-2992.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Quorum Sensing in the Dimorphic Fungus
Candida albicans Is Mediated by Farnesol
Jacob M.
Hornby,1
Ellen C.
Jensen,2
Amber D.
Lisec,1
Joseph J.
Tasto,2,
Brandon
Jahnke,1,
Richard
Shoemaker,3
Patrick
Dussault,3 and
Kenneth
W.
Nickerson1,*
School of Biological Sciences, University of
Nebraska, Lincoln, Nebraska 68588-06661;
Biological Sciences, College of St. Benedict's and St. John's
University, Collegeville, Minnesota 563212; and
Department of Chemistry, University of Nebraska, Lincoln,
Nebraska 68588-03043
Received 31 October 2000/Accepted 26 February 2001
The inoculum size effect in the dimorphic fungus Candida
albicans results from production of an extracellular
quorum-sensing molecule (QSM). This molecule prevents mycelial
development in both a growth morphology assay and a differentiation
assay using three chemically distinct triggers for germ tube formation
(GTF): L-proline, N-acetylglucosamine, and
serum (either pig or fetal bovine). In all cases, the presence of QSM
prevents the yeast-to-mycelium conversion, resulting in actively
budding yeasts without influencing cellular growth rates. QSM exhibits
general cross-reactivity within C. albicans 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°C, in
amounts roughly proportional to the CFU/milliliter. Production is not
dependent on the type of carbon source nor nitrogen source or on the
chemical nature of the growth medium. Both commercial mixed isomer and (E,E)-farnesol exhibited QSM activity (the ability to
prevent GTF) at a level sufficient to account for all the QSM activity present in C. albicans supernatants, i.e., 50% GTF at ca.
30 to 35 µM. Nerolidol was ca. two times less active than farnesol. Neither geraniol (C10), geranylgeraniol (C20),
nor farnesyl pyrophosphate had any QSM activity.
*
Corresponding author. Mailing address: School of
Biological Sciences, University of Nebraska, Lincoln, NE 68588-0666. Phone: (402) 472-2253. Fax: (402) 472-8722. E-mail:
knickerson1{at}unl.edu.

Present address: Cell Biology Department, Vanderbilt University,
Nashville,
Tenn.

Present address: University of Nebraska Medical Center, Omaha,
Nebr.
Applied and Environmental Microbiology, July 2001, p. 2982-2992, Vol. 67, No. 7
0099-2240/01/$04.00+0 DOI: 10.1128/AEM.67.7.2982-2992.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Fleissner, A., Leeder, A. C., Roca, M. G., Read, N. D., Glass, N. L.
(2009). Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion. Proc. Natl. Acad. Sci. USA
106: 19387-19392
[Abstract]
[Full Text]
-
Atkinson, S., Williams, P.
(2009). Quorum sensing and social networking in the microbial world. J R Soc Interface
6: 959-978
[Abstract]
[Full Text]
-
Rennemeier, C., Frambach, T., Hennicke, F., Dietl, J., Staib, P.
(2009). Microbial Quorum-Sensing Molecules Induce Acrosome Loss and Cell Death in Human Spermatozoa. Infect. Immun.
77: 4990-4997
[Abstract]
[Full Text]
-
Chen, F., Liu, X.-M., Rice, K. C., Li, X., Yu, F., Reinhardt, R. A., Bayles, K. W., Wang, D.
(2009). Tooth-Binding Micelles for Dental Caries Prevention. Antimicrob. Agents Chemother.
53: 4898-4902
[Abstract]
[Full Text]
-
Unnanuntana, A., Bonsignore, L., Shirtliff, M. E., Greenfield, E. M.
(2009). The Effects of Farnesol on Staphylococcus aureus Biofilms and Osteoblasts. An in Vitro Study. JBJS
91: 2683-2692
[Abstract]
[Full Text]
-
Jarosz, L. M., Deng, D. M., van der Mei, H. C., Crielaard, W., Krom, B. P.
(2009). Streptococcus mutans Competence-Stimulating Peptide Inhibits Candida albicans Hypha Formation. Eukaryot Cell
8: 1658-1664
[Abstract]
[Full Text]
-
Bamford, C. V., d'Mello, A., Nobbs, A. H., Dutton, L. C., Vickerman, M. M., Jenkinson, H. F.
(2009). Streptococcus gordonii Modulates Candida albicans Biofilm Formation through Intergeneric Communication. Infect. Immun.
77: 3696-3704
[Abstract]
[Full Text]
-
Amaike, S., Keller, N. P.
(2009). Distinct Roles for VeA and LaeA in Development and Pathogenesis of Aspergillus flavus. Eukaryot Cell
8: 1051-1060
[Abstract]
[Full Text]
-
Shirtliff, M. E., Krom, B. P., Meijering, R. A. M., Peters, B. M., Zhu, J., Scheper, M. A., Harris, M. L., Jabra-Rizk, M. A.
(2009). Farnesol-Induced Apoptosis in Candida albicans. Antimicrob. Agents Chemother.
53: 2392-2401
[Abstract]
[Full Text]
-
Paramonova, E., Krom, B. P., van der Mei, H. C., Busscher, H. J., Sharma, P. K.
(2009). Hyphal content determines the compression strength of Candida albicans biofilms. Microbiology
155: 1997-2003
[Abstract]
[Full Text]
-
Ghosh, S., Navarathna, D. H. M. L. P., Roberts, D. D., Cooper, J. T., Atkin, A. L., Petro, T. M., Nickerson, K. W.
(2009). Arginine-Induced Germ Tube Formation in Candida albicans Is Essential for Escape from Murine Macrophage Line RAW 264.7. Infect. Immun.
77: 1596-1605
[Abstract]
[Full Text]
-
ten Cate, J.M., Klis, F.M., Pereira-Cenci, T., Crielaard, W., de Groot, P.W.J.
(2009). Molecular and Cellular Mechanisms That Lead to Candida Biofilm Formation. JDR
88: 105-115
[Abstract]
[Full Text]
-
Cushion, M. T., Collins, M. S., Linke, M. J.
(2009). Biofilm Formation by Pneumocystis spp.. Eukaryot Cell
8: 197-206
[Abstract]
[Full Text]
-
Ghosh, S., Kebaara, B. W., Atkin, A. L., Nickerson, K. W.
(2008). Regulation of Aromatic Alcohol Production in Candida albicans. Appl. Environ. Microbiol.
74: 7211-7218
[Abstract]
[Full Text]
-
Trofa, D., Gacser, A., Nosanchuk, J. D.
(2008). Candida parapsilosis, an Emerging Fungal Pathogen. Clin. Microbiol. Rev.
21: 606-625
[Abstract]
[Full Text]
-
Peleg, A. Y., Tampakakis, E., Fuchs, B. B., Eliopoulos, G. M., Moellering, R. C. Jr., Mylonakis, E.
(2008). Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA
105: 14585-14590
[Abstract]
[Full Text]
-
Clement, M., Tremblay, J., Lange, M., Thibodeau, J., Belhumeur, P.
(2008). Purification and Identification of Bovine Cheese Whey Fatty Acids Exhibiting In Vitro Antifungal Activity. J DAIRY SCI
91: 2535-2544
[Abstract]
[Full Text]
-
Kebaara, B. W., Langford, M. L., Navarathna, D. H. M. L. P., Dumitru, R., Nickerson, K. W., Atkin, A. L.
(2008). Candida albicans Tup1 Is Involved in Farnesol-Mediated Inhibition of Filamentous-Growth Induction. Eukaryot Cell
7: 980-987
[Abstract]
[Full Text]
-
Weber, K., Sohr, R., Schulz, B., Fleischhacker, M., Ruhnke, M.
(2008). Secretion of E,E-Farnesol and Biofilm Formation in Eight Different Candida Species. Antimicrob. Agents Chemother.
52: 1859-1861
[Abstract]
[Full Text]
-
McAlester, G., O'Gara, F., Morrissey, J. P.
(2008). Signal-mediated interactions between Pseudomonas aeruginosa and Candida albicans. J Med Microbiol
57: 563-569
[Abstract]
[Full Text]
-
Martins, M., Henriques, M., Azeredo, J., Rocha, S. M., Coimbra, M. A., Oliveira, R.
(2007). Morphogenesis Control in Candida albicans and Candida dubliniensis through Signaling Molecules Produced by Planktonic and Biofilm Cells. Eukaryot Cell
6: 2429-2436
[Abstract]
[Full Text]
-
Gori, K., Mortensen, H. D., Arneborg, N., Jespersen, L.
(2007). Ammonia Production and Its Possible Role as a Mediator of Communication for Debaryomyces hansenii and Other Cheese-Relevant Yeast Species. J DAIRY SCI
90: 5032-5041
[Abstract]
[Full Text]
-
Navarathna, D. H. M. L. P., Nickerson, K. W., Duhamel, G. E., Jerrels, T. R., Petro, T. M.
(2007). Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model. Infect. Immun.
75: 4006-4011
[Abstract]
[Full Text]
-
Dong, Y.-H., Wang, L.-H., Zhang, L.-H.
(2007). Quorum-quenching microbial infections: mechanisms and implications. Phil Trans R Soc B
362: 1201-1211
[Abstract]
[Full Text]
-
Rossignol, T., Logue, M. E., Reynolds, K., Grenon, M., Lowndes, N. F., Butler, G.
(2007). Transcriptional Response of Candida parapsilosis following Exposure to Farnesol. Antimicrob. Agents Chemother.
51: 2304-2312
[Abstract]
[Full Text]
-
Perumal, P., Mekala, S., Chaffin, W. L.
(2007). Role for Cell Density in Antifungal Drug Resistance in Candida albicans Biofilms. Antimicrob. Agents Chemother.
51: 2454-2463
[Abstract]
[Full Text]
-
Ikeda, R., Saito, F., Matsuo, M., Kurokawa, K., Sekimizu, K., Yamaguchi, M., Kawamoto, S.
(2007). Contribution of the Mannan Backbone of Cryptococcal Glucuronoxylomannan and a Glycolytic Enzyme of Staphylococcus aureus to Contact-Mediated Killing of Cryptococcus neoformans. J. Bacteriol.
189: 4815-4826
[Abstract]
[Full Text]
-
Biswas, S., Van Dijck, P., Datta, A.
(2007). Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans. Microbiol. Mol. Biol. Rev.
71: 348-376
[Abstract]
[Full Text]
-
Navarathna, D. H. M. L. P., Hornby, J. M., Krishnan, N., Parkhurst, A., Duhamel, G. E., Nickerson, K. W.
(2007). Effect of Farnesol on a Mouse Model of Systemic Candidiasis, Determined by Use of a DPP3 Knockout Mutant of Candida albicans. Infect. Immun.
75: 1609-1618
[Abstract]
[Full Text]
-
Dumitru, R., Navarathna, D. H. M. L. P., Semighini, C. P., Elowsky, C. G., Dumitru, R. V., Dignard, D., Whiteway, M., Atkin, A. L., Nickerson, K. W.
(2007). In Vivo and In Vitro Anaerobic Mating in Candida albicans. Eukaryot Cell
6: 465-472
[Abstract]
[Full Text]
-
Alem, M. A. S., Oteef, M. D. Y., Flowers, T. H., Douglas, L. J.
(2006). Production of Tyrosol by Candida albicans Biofilms and Its Role in Quorum Sensing and Biofilm Development. Eukaryot Cell
5: 1770-1779
[Abstract]
[Full Text]
-
Ndagijimana, M., Vallicelli, M., Cocconcelli, P. S., Cappa, F., Patrignani, F., Lanciotti, R., Guerzoni, M. E.
(2006). Two 2[5H]-Furanones as Possible Signaling Molecules in Lactobacillus helveticus. Appl. Environ. Microbiol.
72: 6053-6061
[Abstract]
[Full Text]
-
Li, L., Borkovich, K. A.
(2006). GPR-4 Is a Predicted G-Protein-Coupled Receptor Required for Carbon Source-Dependent Asexual Growth and Development in Neurospora crassa.. Eukaryot Cell
5: 1287-1300
[Abstract]
[Full Text]
-
Nickerson, K. W., Atkin, A. L., Hornby, J. M.
(2006). Quorum sensing in dimorphic fungi: farnesol and beyond.. Appl. Environ. Microbiol.
72: 3805-3813
[Full Text]
-
Sprague, G. F. Jr., Winans, S. C.
(2006). Eukaryotes learn how to count: quorum sensing by yeast.. Genes Dev.
20: 1045-1049
[Full Text]
-
Chen, H., Fink, G. R.
(2006). Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev.
20: 1150-1161
[Abstract]
[Full Text]
-
Monge, R. A., Roman, E., Nombela, C., Pla, J.
(2006). The MAP kinase signal transduction network in Candida albicans.. Microbiology
152: 905-912
[Abstract]
[Full Text]
-
Hogan, D. A.
(2006). Talking to themselves: autoregulation and quorum sensing in fungi.. Eukaryot Cell
5: 613-619
[Full Text]
-
Roman, E., Nombela, C., Pla, J.
(2005). The Sho1 Adaptor Protein Links Oxidative Stress to Morphogenesis and Cell Wall Biosynthesis in the Fungal Pathogen Candida albicans. Mol. Cell. Biol.
25: 10611-10627
[Abstract]
[Full Text]
-
Navarathna, D. H. M. L. P., Hornby, J. M., Hoerrmann, N., Parkhurst, A. M., Duhamel, G. E., Nickerson, K. W.
(2005). Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. J Antimicrob Chemother
56: 1156-1159
[Abstract]
[Full Text]
-
Alem, M. A., Douglas, L J.
(2005). Prostaglandin production during growth of Candida albicans biofilms. J Med Microbiol
54: 1001-1005
[Abstract]
[Full Text]
-
Westwater, C., Balish, E., Schofield, D. A.
(2005). Candida albicans-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance. Eukaryot Cell
4: 1654-1661
[Abstract]
[Full Text]
-
Visick, K. L., Fuqua, C.
(2005). Decoding Microbial Chatter: Cell-Cell Communication in Bacteria. J. Bacteriol.
187: 5507-5519
[Full Text]
-
Mosel, D. D., Dumitru, R., Hornby, J. M., Atkin, A. L., Nickerson, K. W.
(2005). Farnesol Concentrations Required To Block Germ Tube Formation in Candida albicans in the Presence and Absence of Serum. Appl. Environ. Microbiol.
71: 4938-4940
[Abstract]
[Full Text]
-
Martin, S. W., Douglas, L. M., Konopka, J. B.
(2005). Cell Cycle Dynamics and Quorum Sensing in Candida albicans Chlamydospores Are Distinct from Budding and Hyphal Growth. Eukaryot Cell
4: 1191-1202
[Abstract]
[Full Text]
-
Enjalbert, B., Whiteway, M.
(2005). Release from Quorum-Sensing Molecules Triggers Hyphal Formation during Candida albicans Resumption of Growth. Eukaryot Cell
4: 1203-1210
[Abstract]
[Full Text]
-
Laffey, S. F., Butler, G.
(2005). Phenotype switching affects biofilm formation by Candida parapsilosis. Microbiology
151: 1073-1081
[Abstract]
[Full Text]
-
Ramage, G., Saville, S. P., Thomas, D. P., Lopez-Ribot, J. L.
(2005). Candida Biofilms: an Update. Eukaryot Cell
4: 633-638
[Full Text]
-
Cao, Y.-Y., Cao, Y.-B., Xu, Z., Ying, K., Li, Y., Xie, Y., Zhu, Z.-Y., Chen, W.-S., Jiang, Y.-Y.
(2005). cDNA Microarray Analysis of Differential Gene Expression in Candida albicans Biofilm Exposed to Farnesol. Antimicrob. Agents Chemother.
49: 584-589
[Abstract]
[Full Text]
-
Smith, D. A., Nicholls, S., Morgan, B. A., Brown, A. J.P., Quinn, J.
(2004). A Conserved Stress-activated Protein Kinase Regulates a Core Stress Response in the Human Pathogen Candida albicans. Mol. Biol. Cell
15: 4179-4190
[Abstract]
[Full Text]
-
Kruppa, M., Krom, B. P., Chauhan, N., Bambach, A. V., Cihlar, R. L., Calderone, R. A.
(2004). The Two-Component Signal Transduction Protein Chk1p Regulates Quorum Sensing in Candida albicans. Eukaryot Cell
3: 1062-1065
[Abstract]
[Full Text]
-
Dumitru, R., Hornby, J. M., Nickerson, K. W.
(2004). Defined Anaerobic Growth Medium for Studying Candida albicans Basic Biology and Resistance to Eight Antifungal Drugs. Antimicrob. Agents Chemother.
48: 2350-2354
[Abstract]
[Full Text]
-
Hornby, J. M., Nickerson, K. W.
(2004). Enhanced Production of Farnesol by Candida albicans Treated with Four Azoles. Antimicrob. Agents Chemother.
48: 2305-2307
[Abstract]
[Full Text]
-
Martin, S. W., Konopka, J. B.
(2004). Lipid Raft Polarization Contributes to Hyphal Growth in Candida albicans. Eukaryot Cell
3: 675-684
[Abstract]
[Full Text]
-
Chen, H., Fujita, M., Feng, Q., Clardy, J., Fink, G. R.
(2004). Tyrosol is a quorum-sensing molecule in Candida albicans. Proc. Natl. Acad. Sci. USA
101: 5048-5052
[Abstract]
[Full Text]
-
Hornby, J. M., Jacobitz-Kizzier, S. M., McNeel, D. J., Jensen, E. C., Treves, D. S., Nickerson, K. W.
(2004). Inoculum Size Effect in Dimorphic Fungi: Extracellular Control of Yeast-Mycelium Dimorphism in Ceratocystis ulmi. Appl. Environ. Microbiol.
70: 1356-1359
[Abstract]
[Full Text]
-
Care, A., Vousden, K. A., Binley, K. M., Radcliffe, P., Trevethick, J., Mannazzu, I., Sudbery, P. E.
(2004). A Synthetic Lethal Screen Identifies a Role for the Cortical Actin Patch/Endocytosis Complex in the Response to Nutrient Deprivation in Saccharomyces cerevisiae. Genetics
166: 707-719
[Abstract]
[Full Text]
-
Alem, M. A. S., Douglas, L. J.
(2004). Effects of Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs on Biofilms and Planktonic Cells of Candida albicans. Antimicrob. Agents Chemother.
48: 41-47
[Abstract]
[Full Text]
-
Giles, S., Czuprynski, C.
(2003). Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth of Blastomyces dermatitidis Yeast Form In Vitro. Infect. Immun.
71: 6648-6652
[Abstract]
[Full Text]
-
Brehm-Stecher, B. F., Johnson, E. A.
(2003). Sensitization of Staphylococcus aureus and Escherichia coli to Antibiotics by the Sesquiterpenoids Nerolidol, Farnesol, Bisabolol, and Apritone. Antimicrob. Agents Chemother.
47: 3357-3360
[Abstract]
[Full Text]
-
Noverr, M. C., Erb-Downward, J. R., Huffnagle, G. B.
(2003). Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes. Clin. Microbiol. Rev.
16: 517-533
[Abstract]
[Full Text]
-
Hornby, J. M., Kebaara, B. W., Nickerson, K. W.
(2003). Farnesol Biosynthesis in Candida albicans: Cellular Response to Sterol Inhibition by Zaragozic Acid B. Antimicrob. Agents Chemother.
47: 2366-2369
[Abstract]
[Full Text]
-
Ramage, G., Saville, S. P., Wickes, B. L., Lopez-Ribot, J. L.
(2002). Inhibition of Candida albicans Biofilm Formation by Farnesol, a Quorum-Sensing Molecule. Appl. Environ. Microbiol.
68: 5459-5463
[Abstract]
[Full Text]
-
Koo, H., Rosalen, P. L., Cury, J. A., Park, Y. K., Bowen, W. H.
(2002). Effects of Compounds Found in Propolis on Streptococcus mutans Growth and on Glucosyltransferase Activity. Antimicrob. Agents Chemother.
46: 1302-1309
[Abstract]
[Full Text]
-
Ekelund, F., Frederiksen, H. B., Ronn, R.
(2002). Population Dynamics of Active and Total Ciliate Populations in Arable Soil Amended with Wheat. Appl. Environ. Microbiol.
68: 1096-1101
[Abstract]
[Full Text]