Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans

Janik, A.; Niewiadomska, Monika; Perlińska-Lenart, Urszula; Lenart, Jacek; Kolakowski, Damian; Skorupińska-Tudek, Karolina; Świeżewska, Ewa; Kruszewska, Joanna S.; Palamarczyk, Grażyna

doi:10.3390/ijms20205067

Cited by 4 publications

(3 citation statements)

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“…In addition, RER2 mutants are sensitive to antifungal agents [106]. Finally, CWH8 encodes a dolichol pyrophosphate phosphatase that acts as a carbohydrate transporter during N-linked glycosylation and is responsible for converting dolichol pyrophosphate to dolichol phosphate in fungi [107]. Gene deletion disrupted this recycling pathway and pleiotropically affected the cell phenotype [107].…”

Section: Relevance Of N-linked Glycosylations During Host-pathogen Interactionmentioning

confidence: 99%

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Gómez-Gaviria

Vargas-Macías

García-Carnero

et al. 2021

JoF

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Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.

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Section: Relevance Of N-linked Glycosylations During Host-pathogen Interactionmentioning

confidence: 99%

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Gómez-Gaviria

Vargas-Macías

García-Carnero

et al. 2021

JoF

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“…There were 14 DEGs in the N-glycan biosynthesis pathway, 10 of which are involved in mannan synthesis and up-regulated at S3 ( Supplementary Figure 9 and Supplementary Tables 11 , 22 ). For example, dolichyldiphosphatase catalyzes dolichyl diphosphate into dolichol phosphate, the first step of the N-glycan synthesis reaction ( Janik et al, 2019 ). The gene encoding dolichyldiphosphatase was significantly up-regulated at S3.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Dynamics Underlying Chlamydospore Formation in Trichoderma virens GV29-8

Peng

Zhang

et al. 2021

Front. Microbiol.

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Trichoderma spp. are widely used biocontrol agents which are antagonistic to a variety of plant pathogens. Chlamydospores are a type of propagules produced by many fungi that have thick walls and are highly resistant to adverse environmental conditions. Chlamydospore preparations of Trichoderma spp. can withstand various storage conditions, have a longer shelf life than conidial preparations and have better application potential. However, large-scale production of chlamydospores has proven difficult. To understand the molecular mechanisms governing chlamydospore formation (CF) in Trichoderma fungi, we performed a comprehensive analysis of transcriptome dynamics during CF across 8 different developmental time points, which were divided into 4 stages according to PCA analysis: the mycelium growth stage (S1), early and middle stage of CF (S2), flourishing stage of CF (S3), and late stage of CF and mycelia initial autolysis (S4). 2864, 3206, and 3630 DEGs were screened from S2 vs S1, S3 vs S2, and S4 vs S3, respectively. We then identified the pathways and genes that play important roles in each stage of CF by GO, KEGG, STC and WGCNA analysis. The results showed that DEGs in the S2 vs S1 were mainly enriched in organonitrogen compound metabolism, those in S3 vs S2 were mainly involved in secondary metabolite, cell cycle, and N-glycan biosynthesis, and DEGs in S4 vs S3 were mainly involved in lipid, glycogen, and chitin metabolic processes. We speculated that mycelial assimilation and absorption of exogenous nitrogen in the early growth stage (S1), resulted in subsequent nitrogen deficiency (S2). At the same time, secondary metabolites and active oxygen free radicals released during mycelial growth produced an adverse growth environment. The resulting nitrogen-deficient and toxin enriched medium may stimulate cell differentiation by initiating cell cycle regulation to induce morphological transformation of mycelia into chlamydospores. High expression of genes relating to glycogen, lipid, mannan, and chitin synthetic metabolic pathways during the flourishing (S3) and late stages (S4) of CF may be conducive to energy storage and cell wall construction in chlamydospores. For further verifying the functions of the amino sugar and nucleotide sugar metabolism (tre00520) pathway in the CF of T. virens GV29-8 strain, the chitin synthase gene (TRIVIDRAFT_90152), one key gene of the pathway, was deleted and resulted in the dysplasia of mycelia and an incapability to form normal chlamydospores, which illustrated the pathway affecting the CF of T. virens GV29-8 strain. Our results provide a new perspective for understanding the genetics of biochemical pathways involved in CF of Trichoderma spp.

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“…C. albicans SC5314 and CAI4 were grown in the YPD medium (1% yeast extract, 2% peptone, and 2% dextrose) at 30 • C with shaking (150 rpm) under aerobic conditions. A C. albicans DCR1 low-expressing strain (DCR1/dcr1 ) was constructed by deleting one copy of the DCR1 gene using plasmid p5921 according to the URA-Blaster method (Janik et al, 2019). Upstream and downstream fragments of DCR1 from the chromosome were inserted into both ends of the hisG-URA3-hisG cassette of p5921 to obtain the recombinant plasmid pUC-DCR1-URA3 to replace one of the DCR1 alleles in C. albicans.…”

Section: Microorganisms and Construction Of Mutant Strainsmentioning

confidence: 99%

RNase III coding genes modulate the cross-kingdom biofilm of Streptococcus mutans and Candida albicans

Lei²,

Deng³

et al. 2022

Front. Microbiol.

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Streptococcus mutans constantly coexists with Candida albicans in plaque biofilms of early childhood caries (ECC). The progression of ECC can be influenced by the interactions between S. mutans and C. albicans through exopolysaccharides (EPS). Our previous studies have shown that rnc, the gene encoding ribonuclease III (RNase III), is implicated in the cariogenicity of S. mutans by regulating EPS metabolism. The DCR1 gene in C. albicans encodes the sole functional RNase III and is capable of producing non-coding RNAs. However, whether rnc or DCR1 can regulate the structure or cariogenic virulence of the cross-kingdom biofilm of S. mutans and C. albicans is not yet well understood. By using gene disruption or overexpression assays, this study aims to investigate the roles of rnc and DCR1 in modulating the biological characteristics of dual-species biofilms of S. mutans and C. albicans and to reveal the molecular mechanism of regulation. The morphology, biomass, EPS content, and lactic acid production of the dual-species biofilm were assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and transcriptomic profiling were performed to unravel the alteration of C. albicans virulence. We found that both rnc and DCR1 could regulate the biological traits of cross-kingdom biofilms. The rnc gene prominently contributed to the formation of dual-species biofilms by positively modulating the extracellular polysaccharide synthesis, leading to increased biomass, biofilm roughness, and acid production. Changes in the microecological system probably impacted the virulence as well as polysaccharide or pyruvate metabolism pathways of C. albicans, which facilitated the assembly of a cariogenic cross-kingdom biofilm and the generation of an augmented acidic milieu. These results may provide an avenue for exploring new targets for the effective prevention and treatment of ECC.

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Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans

Cited by 4 publications

References 57 publications

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Transcriptome Dynamics Underlying Chlamydospore Formation in Trichoderma virens GV29-8

RNase III coding genes modulate the cross-kingdom biofilm of Streptococcus mutans and Candida albicans

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