Candida albicans adapts to toxic levels of the quorum sensing molecule farnesol through cell wall remodeling
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE192686 | GEO | 2026/07/21
REPOSITORIES: GEO
Similar Datasets
Project description:In the opportunistic pathogen Candida albicans, hyphal growth and virulence factor expression are regulated by environmental and chemical cues. Farnesol is a secreted autoregulatory molecule that represses filamentation. It is derived from farnesyl pyrophosphate (FPP), an ergosterol biosynthesis pathway intermediate. Although Dpp1, Dpp2, and Dpp3 were proposed to synthesize farnesol, a mutant lacking all three had only a modest reduction in farnesol. To identify other farnesol biosynthesis genes, we employed transcription factor mutants that underproduced or overproduced farnesol in a screen and analyzed their transcriptomes. CWH8 was the only transcript correlated with farnesol production. Cwh8 is a lipid phosphatase known to recycle dolichyl pyrophosphate during glycosylation of cell wall proteins. The cwh8ΔΔ mutant had a >99% reduction in farnesol compared to the parent strain and was hyperfilamentous in embedded conditions. It had ~900-fold lower levels of farnesyl phosphate, the product of FPP dephosphorylation, suggesting Cwh8 acts directly on FPP. Complementation of the C. albicans cwh8ΔΔ mutant with CWH8 from C. albicans restored cell wall integrity and farnesol production. However, complementation with CWH8 from Clavispora lusitaniae, a species lacking farnesol signaling, restored cell wall integrity but failed to rescue farnesol production. This indicates that while Cwh8’s role in maintaining cell wall integrity is conserved, differences in substrate specificity or interactions with species-specific cofactors underlie its involvement in farnesol biosynthesis in C. albicans. Finally, fluconazole was fungicidal for cwh8ΔΔ rather than fungistatic. These studies demonstrate how an extracellular signaling system can arise and be co-opted to promote fungal fitness in complex environments.
2025-08-26 | GSE289051 | GEO
Project description:Protein glycolysation is an essential posttranslational modification in eukaryotic cells. In pathogenic yeasts, it is involved in a large number of biological processes, such as protein folding quality control, cell viability and host/pathogen relationships. A link between protein glycosylation and apoptosis was established by the analysis of the phenotypes of oligosaccharyltransferase mutants in budding yeast. However, little is known about the contribution of glycosylation modifications to the adaptive response to apoptosis inducers. The cysteine protease metacaspase Mca1p plays a key role in the apoptotic response in Candida albicans triggered by the quorum sensing molecule farnesol. We subjected wild-type and mca1-deletion strains to farnesol stress and then studied the early phase of apoptosis release in quantitative glycoproteomics and glycomics experiments on cell-free extracts essentially devoid of cell walls. We identified and characterized 62 new glycosylated peptides with their glycan composition: 17 N-glycosylated, 45 O-glycosylated, and 81 additional sites of N-glycosylation. The glycosylated proteins were predicted as located mostly in the “membrane” and “cell wall” compartments, but they were also related to the “nucleus” and the “mitochondrial” compartments. They were found to be involved in the control of protein folding, cell wall integrity and cell cycle regulation. We showed a general increase in the O-glycosylation of proteins in the mca1 deletion strain after farnesol challenge. We identified 44 new putative protein substrates of the metacaspase in the glycoprotein fraction enriched on concanavalin A. Most of these substrates are involved in protein folding or protein resolubilization and in mitochondrial functions. We show here that key Mca1p substrates, such as Cdc48p or Ssb1p, involved in degrading misfolded glycoproteins and in the protein quality control system, are themselves differentially glycosylated. We found putative substrates, such as Bgl2p, Srb1p or Ugp1p, that are involved in the biogenesis of glycans. We validated as a substrate of Mca1p the endo-beta-1,3-glucanase Bgl2p which is involved in the incorporation of newly synthetized mannoproteins in the cell wall. Our findings highlight a new role of the metacaspase in amplifying cell death processes by affecting several critical protein quality control systems through the alteration of the protein glycosylation machinery.
2016-05-02 | PXD003677 | Pride
Project description:Monocytes differentiated in the presence of farnesol from 4 different donors where harvested after 3 and 6 days of differentiation and after exposure to LPS for 6h (at day 6) and analyzed on an Illumina HumanHT-12 v4 Expression BeadChip.
2015-02-20 | E-MTAB-2813 | biostudies-arrayexpress
Project description:Background: Heterotopic ossification (HO), characterized by pathological bone formation in extra-skeletal tissues such as tendon, often results in debilitating tissue dysfunction. HO of tendons primarily arises from abnormal osteogenic differentiation of tendon stem cells following injury. Despite being a common clinical occurrence, the cellular and molecular mechanisms of tendon HO are poorly understood, and effective treatments remain elusive. Farnesol, a natural isoprenoid alcohol abundant in citrus fruits, lavender, and royal jelly, is known for its potent anti-inflammatory, antioxidant, and antitumor properties. However, its applications in tissue engineering are rarely explored, particularly in musculoskeletal repair. Here, we provide the first report on the therapeutic potential of Farnesol in attenuating tendon HO and elucidate the associated molecular mechanisms.Methods: This study evaluated the effects of Farnesol on osteogenic differentiation of tendon-derived stem cells using both in vitro and in vivo models. The molecular mechanisms underlying the therapeutic effects of Farnesol on tendon HO were revealed by RNA sequencing combined with network pharmacology analysis, identifying the GSTP1/MAPK axis as a potential target pathway. In vitro rescue experiments using a specific GSTP1 inhibitor were conducted to confirm whether Farnesol primarily exerted its therapeutic effects through GSTP1.Results: The results demonstrated significant effects of Farnesol on attenuating tendon HO both in vitro and in vivo. Combined analysis of transcriptomics and network pharmacology indicated that Farnesol functions by targeting the GSTP1/MAPK signaling axis. These findings were further validated by in vitro experiments using the GSTP1 inhibitor, which reversed the suppressive effects of Farnesol on osteogenesis.Conclusion: Farnesol inhibits the progression of post-traumatic tendon HO by targeting the GSTP1/MAPK pathway. These findings provide new insights into the potential of using Farnesol as a therapeutic agent for HO.
2026-01-31 | GSE317543 | GEO
Project description:Gene expression profiles of Molt4 cells treated with DMCS (vehicle) or farnesol were compared to understand the mechanism by which farnesol induces apoptosis in these cells.
2014-05-01 | GSE46670 | GEO
Project description:The antifungal resistance threat posed by Candida auris necessitates bold and innovative therapeutic options. Farnesol, a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment regimens. To gain further insights into the farnesol-related effect on C. auris, genome-wide gene expression analysis was performed using RNA-Seq. Farnesol exposure resulted in 1,766 differentially expressed genes. Of these, 447 and 304 genes with at least 1.5-fold increase or decrease in expression, respectively, were selected for further investigation. Genes involved in morphogenesis, biofilm events (maturation and dispersion), gluconeogenesis, iron metabolism, and regulation of RNA biosynthesis showed down-regulation, whereas those related to antioxidative defense, transmembrane transport, glyoxylate cycle, fatty acid β-oxidation, and peroxisome processes were up-regulated. In addition, farnesol treatment increased the expression of certain efflux pump genes, including MDR1, CDR1, and CDR2. Growth, measured by change in CFU number, was significantly inhibited within 2 hours of the addition of farnesol (5.8×10^7±1.1×10^7 and 1.1×10^7±0.3×10^7 CFU/ml for untreated control and farnesol-exposed cells, respectively) (p<0.001). In addition, farnesol treatment caused a significant reduction in intracellular iron (152.2±21.1 vs. 116.0±10.0 mg/kg), manganese (67.9±5.1 vs. 18.6±1.8 mg/kg), and zinc (787.8±22.2 vs. 245.8±34.4 mg/kg) (p<0.05–0.001) compared to untreated control cells, whereas the level of cooper was significantly increased (274.6±15.7 vs. 828.8±106.4 mg/kg) (p<0.001). Our data demonstrate that farnesol significantly influences the growth, intracellular metal ion contents, and gene expression related to fatty acid metabolism, which could open new directions in developing alternative therapies against C. auris.
2021-09-30 | GSE180093 | GEO
Project description:We used the results of a genome sequence survey to design and manufacture partial genomic microarrays that were applied to determining the transcriptional response of C. parapsilosis to the presence of exogenous farnesol. Keywords: drug response, farnesol, Transcriptional profiling was performed following exposure to 50 microM of farnesol compare to the control experiment (no treatment). Six independent experiment comparisons (including 3 dye swaps) were performed.
2010-06-11 | E-GEOD-6318 | biostudies-arrayexpress
Project description:We used the results of a genome sequence survey to design and manufacture partial genomic microarrays that were applied to determining the transcriptional response of C. parapsilosis to the presence of exogenous farnesol. Keywords: drug response, farnesol,
2007-03-01 | GSE6318 | GEO
Project description:Gene expression profiles of Molt4 cells treated with DMCS (vehicle) or farnesol were compared to understand the mechanism by which farnesol induces apoptosis in these cells. Molt4 cells were treated with 75 uM farnesol for 4 hrs to compare with vehicle-treated Molt4 cells. RNA from three replicates for each treatment was then isolated for microarray analysis.
2014-05-01 | E-GEOD-46670 | biostudies-arrayexpress
Project description:Farnesol is a nonsterol isoprenoid produced by dephosphorylation of farnesyl pyrophosphate, a catabolite of the cholesterol biosynthetic pathway. These isoprenoids have been reported to inhibit proliferation and induce apoptosis in neoplastic cell lines as well as to be effective in chemotherapy in several in vivo cancer models. Recently, it was shown that farnesol triggers morphological features characteristic of apoptosis in the filamentous fungus Aspergillus nidulans. In order to investigate which pathways are involved under Farnesol treatment, we determined the transcriptional profile of A. nidulans wild type strain. Conidia were incubated at 37°C in complete medium for 16 hours and were esposed or not to 100 μM Farnesol for 2 hours. The mycelia were harvested by centrifugation and used for competitive microarray hybridizations. We detected differential regulation of genes involved in a variety of cellular processes whose specific modulation is likely to be implicated with A. nidulans adaptation to farnesol. We observed decreased mRNA abundance of several genes involved in RNA processing and modification, transcription, translation, ribosomal structure and biogenesis, amino acid transport and metabolism. Interestingly, several genes involved in the ergosterol biosynthesis (such as the homologues of erg4/24, 11A, -11B, -13, -25, and –28) have decreased mRNA accumulation and other genes encoding mitochondrial proteins [such as AN9103.3, AN4500.3, and AN5440.3, encoding the Apoptosis Inducing Factor (AIF)-like mitochondrial oxidoreductase, the mitochondrial ATPase inhibitor, and the cytochrome c peroxidase, respectively] have increased mRNA expression when A. nidulans was exposed to farnesol. We also observed as more expressed several genes encoding proteins involved in trehalose metabolism and chaperones. Keywords: farnesol effect
2008-03-06 | GSE10712 | GEO