Δ12-Fatty Acid Desaturase from Candida parapsilosis Is a Multifunctional Desaturase Producing a Range of Polyunsaturated and Hydroxylated Fatty Acids

Buček, Aleš; Matoušková, Petra; Sychrová, Hana; Pichová, Iva; Hrušková−Heidingsfeldová, Olga

doi:10.1371/journal.pone.0093322

Cited by 24 publications

(10 citation statements)

References 54 publications

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“…The synthesis of PUFAs is significantly downregulated in tyrosol-treated cells, as tyrosol decreased the expression of the FAD2 and FAD3 genes encoding delta12-fatty acid desaturase and omega-3 fatty acid desaturase enzymes, respectively. These are orthologs of genes participating in PUFA synthesis in C. albicans (16,17). PUFAs (stearidonic acid, eicosapentaenoic acid, and docosapentaenoic acid) are major components of the cell membrane of C. parapsilosis, accounting for approximately 30% of the fatty acid content, and have a remarkable antioxidant effect (17).…”

Section: Discussionmentioning

confidence: 99%

“…These are orthologs of genes participating in PUFA synthesis in C. albicans (16,17). PUFAs (stearidonic acid, eicosapentaenoic acid, and docosapentaenoic acid) are major components of the cell membrane of C. parapsilosis, accounting for approximately 30% of the fatty acid content, and have a remarkable antioxidant effect (17). Tyrosol-induced inhibition of the expression of FAD2 and FAD3 found in this study therefore decreases the antioxidant level in cell membranes, which may contribute to the antifungal effect of tyrosol against C. albicans or C. parapsilosis (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

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Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Jakab

Tóth

Nagy

et al. 2019

Appl Environ Microbiol

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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. IMPORTANCE Candida-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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Jakab

Tóth

Nagy

et al. 2019

Appl Environ Microbiol

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“…Enhanced phagocytosis and killing of ⌬/⌬ole2 cells and the induced increased levels of interleukin-10 (IL-10) suggested that CpOLE2 may also be involved in virulence regulation (136). Although functional Δ12/Δ15-and Δ15-fatty acid desaturases (FAD2 and FAD3) have also been identified in this species, their influence on virulence has not yet been investigated (228).…”

Section: Fatty Acid Metabolismmentioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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SUMMARY Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis’ increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis. Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species’ genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

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“…Yeasts transformed with pYES2 and pYEXTHS-BN were cultivated in liquid YNB medium lacking uracil. Heterologous FAD expression in pYEXTHS-BN transformed yeasts was monitored by Western blotting using anti-His6tag antibodies (37). Total cellular lipids were transesterified to FAMEs (18).…”

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confidence: 99%

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

Buček

Matoušková

Vogel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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For sexual communication, moths primarily use blends of fatty acid derivatives containing one or more double bonds in various positions and configurations, called sex pheromones (SPs). To study the molecular basis of novel SP component (SPC) acquisition, we used the tobacco hornworm (Manduca sexta), which uses a blend of mono-, di-, and uncommon triunsaturated fatty acid (3UFA) derivatives as SP. We identified pheromone-biosynthetic fatty acid desaturases (FADs) MsexD3, MsexD5, and MsexD6 abundantly expressed in the M. sexta female pheromone gland. Their functional characterization and in vivo application of FAD substrates indicated that MsexD3 and MsexD5 biosynthesize 3UFAs via E/Z14 desaturation from diunsaturated fatty acids produced by previously characterized Z11-desaturase/conjugase MsexD2. Site-directed mutagenesis of sequentially highly similar MsexD3 and MsexD2 demonstrated that swapping of a single amino acid in the fatty acyl substrate binding tunnel introduces E/Z14-desaturase specificity to mutated MsexD2. Reconstruction of FAD gene phylogeny indicates that MsexD3 was recruited for biosynthesis of 3UFA SPCs in M. sexta lineage via gene duplication and neofunctionalization, whereas MsexD5 representing an alternative 3UFA-producing FAD has been acquired via activation of a presumably inactive ancestral MsexD5. Our results demonstrate that a change as small as a single amino acid substitution in a FAD enzyme might result in the acquisition of new SP compounds.fatty acid desaturase | Manduca sexta | sex pheromone biosynthesis | pheromone evolution | substrate specificity S ex pheromones (SPs) are a diverse group of chemical compounds that are central to mate-finding behavior in insects (1). Variation in SP composition between closely related species and among populations is well documented. Despite this variation, SPs are presumed to be under strong stabilizing selection, and thus the genetic mechanisms driving SP diversification represented an enigma (2). Research on SPs in moths (Insecta: Lepidoptera) helped establish the hypothesis of asymmetric tracking as a major driving force in SP diversification. In this scenario, abrupt changes in female SP composition via a shift in component ratio or the inclusion or loss of a component result in a distinct SP that attracts males with more broadly or differentially tuned SP preference (3). Assortative mating, the preferential mating of females producing a novel SP with males attracted to this SP, restricts gene flow between subpopulations with differing SP compositions. This can ultimately lead to speciation and fixation of novel communication channels (4). Work in insect models such as wasps (5), fruit flies (6), and especially moths (7-9) is helping uncover the genetic basis of SP diversification.In the majority of moth species, females use species-specific mixtures of SP components (SPCs) consisting of volatile fatty acid (FA) derivatives to attract conspecific males at long range. These SPCs are predominantly long-chain aliphatic (C12-C18) acetates, alcoh...

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Δ12-Fatty Acid Desaturase from Candida parapsilosis Is a Multifunctional Desaturase Producing a Range of Polyunsaturated and Hydroxylated Fatty Acids

Cited by 24 publications

References 54 publications

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Candida parapsilosis: from Genes to the Bedside

Evolution of moth sex pheromone composition by a single amino acid substitution in a fatty acid desaturase

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