Transcriptional profiling of the candida auris response to exogenous farnesol exposure

Ágnes Jakab, Noémi Balla, Ágota Ragyák, Fruzsina Nagy, Fruzsina Kovács, Zsófi Sajtos, Zoltán Tóth, Andrew M. Borman, István Pócsi, Edina Baranyai, ászló Majoros, Renátó Kovács*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The antifungal resistance threat posed by Candida auris necessitates bold and innovative therapeutic options. Farnesol is 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 transcription analysis was performed using transcriptome sequencing (RNA-Seq). Farnesol exposure resulted in 1,766 differentially expressed genes. Of these genes, 447 and 304 genes with at least 1.5-fold increase or decrease in transcription, respectively, were selected for further investigation. Genes involved in morphogenesis, biofilm events (maturation and dispersion), gluconeogenesis, iron metabolism, and regulation of RNA biosynthesis showed downregulation, whereas those related to antioxidative defense, transmembrane transport, glyoxylate cycle, fatty acid b-oxidation, and peroxisome processes were upregulated. In addition, farnesol treatment increased the transcription of certain efflux pump genes, including MDR1, CDR1, and CDR2. Growth, measured by the change in the number of CFU, was significantly inhibited within 2 h of the addition of farnesol (5.8 x 107 ± 1.1 x 107 and 1.1 _ 107 ± 0.3 x 107 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 versus 116.0 ± 10.0 mg/kg), manganese (67.9 ± 5.1 versus 18.6 ± 1.8 mg/ kg), and zinc (787.8 ± 22.2 versus 245.8 ± 34.4 mg/kg) (P < 0.05 to 0.001) compared to untreated control cells, whereas the level of cooper was significantly increased (274.6 ± 15.7 versus 828.8 ± 106.4 mg/kg) (P < 0.001). Our data demonstrate that farnesol significantly influences the growth, intracellular metal ion contents, and gene transcription related to fatty acid metabolism, which could open new directions in developing alternative therapies against C. auris.

Original languageEnglish
Article numbere00710-21
JournalmSphere
Volume6
Issue number5
DOIs
Publication statusPublished - Oct 2021
Externally publishedYes

Bibliographical note

Funding Information:
This project was supported by the EFOP-3.6.3-VEKOP-16-2017-00009 program. This research was funded by the European Union and the European Social (EFOP-3.6.1-16-2016-00022) by the Thematic Excellence Programme (TKP2020-IKA-04) of the Ministry for Innovation and Technology in Hungary. This research was funded by the Hungarian National Research, Development and Innovation Office (NKFIH FK138462) (R. Kovács). R. Kovács was supported by OTKA Bridging Fund and FEMS Research and Training Grant (FEMS-GO-2019-502). R. Kovács was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. F. Nagy was supported by the ÚNKP-19-3 and ÚNKP-20-3 New National Excellence Program of the Ministry for Innovation and Technology.

Funding Information:
L. Majoros received conference travel grants from MSD, Astellas, and Pfizer. All other authors declare no conflicts of interest.

Publisher Copyright:
© 2021 American Society for Microbiology. All rights reserved.

Keywords

  • Candida auris
  • Copper
  • Farnesol
  • Iron
  • Metal
  • Oxidative stress
  • Quorum sensing
  • Transcriptome analysis
  • Zinc

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