Farnesol-induced apoptosis in Candida albicans

Mark E. Shirtliff, Bastiaan P. Krom, Roelien A.M. Meijering, Brian Peters, Jingsong Zhu, Mark A. Scheper, Megan L. Harris, Mary Ann Jabra-Rizk

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Abstract

Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase- mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival.

Original languageEnglish (US)
Pages (from-to)2392-2401
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2009

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Farnesol
Candida albicans
Apoptosis
Caspases
Electron Transport
Proteins
Mitochondrial Degradation
Quorum Sensing
DNA Nucleotidylexotransferase
Mitochondrial Proteins
Terpenes
Conservation of Natural Resources
In Situ Nick-End Labeling
Sterols
Glycolysis
Biofilms
Biotin
Germination
Life Cycle Stages
Actin Cytoskeleton

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Shirtliff, M. E., Krom, B. P., Meijering, R. A. M., Peters, B., Zhu, J., Scheper, M. A., ... Jabra-Rizk, M. A. (2009). Farnesol-induced apoptosis in Candida albicans. Antimicrobial Agents and Chemotherapy, 53(6), 2392-2401. https://doi.org/10.1128/AAC.01551-08

Farnesol-induced apoptosis in Candida albicans. / Shirtliff, Mark E.; Krom, Bastiaan P.; Meijering, Roelien A.M.; Peters, Brian; Zhu, Jingsong; Scheper, Mark A.; Harris, Megan L.; Jabra-Rizk, Mary Ann.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 6, 01.06.2009, p. 2392-2401.

Research output: Contribution to journalArticle

Shirtliff, ME, Krom, BP, Meijering, RAM, Peters, B, Zhu, J, Scheper, MA, Harris, ML & Jabra-Rizk, MA 2009, 'Farnesol-induced apoptosis in Candida albicans', Antimicrobial Agents and Chemotherapy, vol. 53, no. 6, pp. 2392-2401. https://doi.org/10.1128/AAC.01551-08
Shirtliff ME, Krom BP, Meijering RAM, Peters B, Zhu J, Scheper MA et al. Farnesol-induced apoptosis in Candida albicans. Antimicrobial Agents and Chemotherapy. 2009 Jun 1;53(6):2392-2401. https://doi.org/10.1128/AAC.01551-08
Shirtliff, Mark E. ; Krom, Bastiaan P. ; Meijering, Roelien A.M. ; Peters, Brian ; Zhu, Jingsong ; Scheper, Mark A. ; Harris, Megan L. ; Jabra-Rizk, Mary Ann. / Farnesol-induced apoptosis in Candida albicans. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 6. pp. 2392-2401.
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