Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Ágnes Jakab, Zoltán Tóth, Fruzsina Nagy, Dániel Nemes, I. Bácskay, G. Kardos, T. Emri, I. Pócsi, László Majoros, Renátó Kovács

Research output: Contribution to journalArticle

Abstract

Tyrosol plays a key role in fungal morphogenesis and biofilm development. Also, it has a remarkable antifungal effect at supraphysiological concentrations. However, the background of the antifungal effect remains unknown, especially in the case of non-albicans Candida species such as Candida parapsilosis We examined the effect of tyrosol on growth, adhesion, redox homeostasis, virulence, as well as fluconazole susceptibility. To gain further insights into the physiological consequences of tyrosol treatment, we also determined genome-wide gene expression changes using transcriptome sequencing (RNA-Seq). A concentration of 15 mM tyrosol caused significant growth inhibition within 2 h of the addition of tyrosol, while the adhesion of yeast cells was not affected. Tyrosol increased the production of reactive oxygen species remarkably, as revealed by a dichlorofluorescein test, and it was associated with elevated superoxide dismutase, glutathione peroxidase, and catalase activities. The interaction between fluconazole and tyrosol was antagonistic. Tyrosol exposure resulted in 261 and 181 differentially expressed genes with at least a 1.5-fold increase or decrease in expression, respectively, which were selected for further study. Genes involved in ribosome biogenesis showed downregulation, while genes related to the oxidative stress response and ethanol fermentation were upregulated. In addition, tyrosol treatment upregulated the expression of efflux pump genes, including MDR1 and CDR1, and downregulated the expression of the FAD2 and FAD3 virulence genes involved in desaturated fatty acid formation. Our data demonstrate that exogenous tyrosol significantly affects the physiology and gene expression of C. parapsilosis, which could contribute to the development of treatments targeting quorum sensing in the future.IMPORTANCECandida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) are key regulators in fungal physiology, which induce phenotypic adaptations, including morphological changes, altered biofilm formation, and synchronized expression of virulence factors. Moreover, they have a remarkable antifungal activity at supraphysiological concentrations. Limited data are available concerning the tyrosol-induced molecular and physiological effects on non-albicans Candida species such as C. parapsilosis In addition, the background of the previously observed antifungal effect caused by tyrosol remains unknown. This study reveals that tyrosol exposure enhanced the oxidative stress response and the expression of efflux pump genes, while it inhibited growth and ribosome biogenesis as well as several virulence-related genes. Metabolism was changed toward glycolysis and ethanol fermentation. Furthermore, the initial adherence was not influenced significantly in the presence of tyrosol. Our results provide several potential explanations for the previously observed antifungal effect.

Original languageEnglish
JournalApplied and environmental microbiology
Volume85
Issue number20
DOIs
Publication statusPublished - Oct 15 2019

Fingerprint

Candida parapsilosis
Candida
virulence
gene
genes
ethanol fermentation
fluconazole
quorum sensing
ribosomes
adhesion
biofilm
fermentation
gene expression
physiology
transporters
ethanol
stress response
pump
fungus physiology
oxidative stress

Keywords

  • Candida parapsilosis
  • oxidative stress
  • quorum sensing
  • RNA-Seq
  • tyrosol

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

Cite this

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol. / Jakab, Ágnes; Tóth, Zoltán; Nagy, Fruzsina; Nemes, Dániel; Bácskay, I.; Kardos, G.; Emri, T.; Pócsi, I.; Majoros, László; Kovács, Renátó.

In: Applied and environmental microbiology, Vol. 85, No. 20, 15.10.2019.

Research output: Contribution to journalArticle

Jakab, Ágnes ; Tóth, Zoltán ; Nagy, Fruzsina ; Nemes, Dániel ; Bácskay, I. ; Kardos, G. ; Emri, T. ; Pócsi, I. ; Majoros, László ; Kovács, Renátó. / Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol. In: Applied and environmental microbiology. 2019 ; Vol. 85, No. 20.
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AU - Bácskay, I.

AU - Kardos, G.

AU - Emri, T.

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N2 - Tyrosol plays a key role in fungal morphogenesis and biofilm development. Also, it has a remarkable antifungal effect at supraphysiological concentrations. However, the background of the antifungal effect remains unknown, especially in the case of non-albicans Candida species such as Candida parapsilosis We examined the effect of tyrosol on growth, adhesion, redox homeostasis, virulence, as well as fluconazole susceptibility. To gain further insights into the physiological consequences of tyrosol treatment, we also determined genome-wide gene expression changes using transcriptome sequencing (RNA-Seq). A concentration of 15 mM tyrosol caused significant growth inhibition within 2 h of the addition of tyrosol, while the adhesion of yeast cells was not affected. Tyrosol increased the production of reactive oxygen species remarkably, as revealed by a dichlorofluorescein test, and it was associated with elevated superoxide dismutase, glutathione peroxidase, and catalase activities. The interaction between fluconazole and tyrosol was antagonistic. Tyrosol exposure resulted in 261 and 181 differentially expressed genes with at least a 1.5-fold increase or decrease in expression, respectively, which were selected for further study. Genes involved in ribosome biogenesis showed downregulation, while genes related to the oxidative stress response and ethanol fermentation were upregulated. In addition, tyrosol treatment upregulated the expression of efflux pump genes, including MDR1 and CDR1, and downregulated the expression of the FAD2 and FAD3 virulence genes involved in desaturated fatty acid formation. Our data demonstrate that exogenous tyrosol significantly affects the physiology and gene expression of C. parapsilosis, which could contribute to the development of treatments targeting quorum sensing in the future.IMPORTANCECandida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) are key regulators in fungal physiology, which induce phenotypic adaptations, including morphological changes, altered biofilm formation, and synchronized expression of virulence factors. Moreover, they have a remarkable antifungal activity at supraphysiological concentrations. Limited data are available concerning the tyrosol-induced molecular and physiological effects on non-albicans Candida species such as C. parapsilosis In addition, the background of the previously observed antifungal effect caused by tyrosol remains unknown. This study reveals that tyrosol exposure enhanced the oxidative stress response and the expression of efflux pump genes, while it inhibited growth and ribosome biogenesis as well as several virulence-related genes. Metabolism was changed toward glycolysis and ethanol fermentation. Furthermore, the initial adherence was not influenced significantly in the presence of tyrosol. Our results provide several potential explanations for the previously observed antifungal effect.

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