Farnesol-induced apoptosis in Candida albicans
| Autor: | Mark A. Scheper, Roelien A. M. Meijering, Bastiaan P. Krom, Mary Ann Jabra-Rizk, Megan L. Harris, Brian M. Peters, Jingsong Zhu, Mark E. Shirtliff |
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| Přispěvatelé: | University of Groningen, Preventive Dentistry |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Proteome
Respiratory chain Apoptosis SACCHAROMYCES-CEREVISIAE chemistry.chemical_compound FUNCTIONAL-CHARACTERIZATION Candida albicans/cytology Candida albicans Pharmacology (medical) REAL-TIME PCR Fungal Proteins/analysis Caspase GENE-EXPRESSION Guanine Nucleotide Dissociation Inhibitors biology STATIONARY-PHASE Farnesol Cell biology Mitochondria Infectious Diseases Biochemistry Caspases Guanine Nucleotide Dissociation Inhibitors/physiology lipids (amino acids peptides and proteins) Drug Programmed cell death Caspases/genetics Fungal Proteins Dose-Response Relationship GDP DISSOCIATION INHIBITOR Reactive Oxygen Species/metabolism AUTOREGULATORY SUBSTANCE Mitochondria/metabolism In Situ Nick-End Labeling rho-Specific Guanine Nucleotide Dissociation Inhibitors STRESS-RESPONSE Mechanisms of Action: Physiological Effects Pharmacology Dose-Response Relationship Drug Actin cytoskeleton reorganization BIOFILM FORMATION Apoptosis/drug effects Caspase Gene biology.organism_classification chemistry Farnesol/pharmacology biology.protein QUORUM-SENSING MOLECULE Reactive Oxygen Species |
| Zdroj: | 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 ', Antimicrobial agents and chemotherapy, vol. 53, no. 6, pp. 2392-401 . https://doi.org/10.1128/AAC.01551-08 Antimicrobial Agents and Chemotherapy, 53(6), 2392-2401. AMER SOC MICROBIOLOGY Antimicrobial agents and chemotherapy, 53(6), 2392-401. American Society for Microbiology |
| ISSN: | 0066-4804 |
| DOI: | 10.1128/AAC.01551-08 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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