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The transcriptional stress response of Candida albicans to weak organic acids.

Cottier F, Tan AS, Chen J, Lum J, Zolezzi F, Poidinger M, Pavelka N - G3 (Bethesda) (2015)

Bottom Line: Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations.Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels and of ribosomal RNA in particular.In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

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Global transcriptome changes induced by weak organic acids (WOAs) in Candida albicans: (A) Principal component analysis of the entire transcriptome dataset of 6453 transcripts across 89 conditions. Samples are plotted by their first two principal components. The first letter of the sample name represents the treatment (C: De Man, Rogosa, and Sharpe medium [MRS] control, H: HCl, L: lactic, A: acetic, P: propionic, B: butyric acid), the middle number represents the time point (1: T1, 2: T2, 3: T3, 4: T4), whereas the last letter refers to the biological replicate (B, C, D, or F). (B) Hierarchical clustering of Gene Ontology (GO) Biological Process terms based on their enrichment in lists of genes differentially expressed in response to individual WOAs and individual time points. Before enrichment analysis, differentially expressed gene lists were removed of genes also significantly modulated in HCl-treated vs. untreated cells. The heat map is color-coded based on Bonferroni-corrected P values, as indicated by the color bar at the bottom. Only GO terms with an adjusted P value < 5 × 10−4 in at least one of the 16 conditions were included in the heat map. Related GO terms are color-coded based on the more general functional category indicated on the right. Distance metric: Euclidean.
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fig2: Global transcriptome changes induced by weak organic acids (WOAs) in Candida albicans: (A) Principal component analysis of the entire transcriptome dataset of 6453 transcripts across 89 conditions. Samples are plotted by their first two principal components. The first letter of the sample name represents the treatment (C: De Man, Rogosa, and Sharpe medium [MRS] control, H: HCl, L: lactic, A: acetic, P: propionic, B: butyric acid), the middle number represents the time point (1: T1, 2: T2, 3: T3, 4: T4), whereas the last letter refers to the biological replicate (B, C, D, or F). (B) Hierarchical clustering of Gene Ontology (GO) Biological Process terms based on their enrichment in lists of genes differentially expressed in response to individual WOAs and individual time points. Before enrichment analysis, differentially expressed gene lists were removed of genes also significantly modulated in HCl-treated vs. untreated cells. The heat map is color-coded based on Bonferroni-corrected P values, as indicated by the color bar at the bottom. Only GO terms with an adjusted P value < 5 × 10−4 in at least one of the 16 conditions were included in the heat map. Related GO terms are color-coded based on the more general functional category indicated on the right. Distance metric: Euclidean.

Mentions: Unsupervised principal component analysis (Figure 2A) and hierarchical clustering (Figure S2) of the 89 analyzed samples led to the following observations. Consistent with the effect on the OD of the cultures (Figure 1B), the HCl-treated samples clustered more closely with the untreated samples than with any other samples, indicating that the effect exerted by WOAs on C. albicans goes beyond a mere response to acidification of the media. Lactic acid−treated samples formed a cluster by themselves that was relatively compact through time, suggesting a unique cellular response to this acid. Acetic acid−treated cells were closer to control cells at T1 but clustered away from all other samples at T3 and T4, indicating a distinct feature in the transcriptional response of C. albicans to this particular acid especially under chronic exposure. Also, propionic and butyric acid displayed a differential behavior between T1 and subsequent time points; however, they also were consistently more similar to each other than to any other treatment.


The transcriptional stress response of Candida albicans to weak organic acids.

Cottier F, Tan AS, Chen J, Lum J, Zolezzi F, Poidinger M, Pavelka N - G3 (Bethesda) (2015)

Global transcriptome changes induced by weak organic acids (WOAs) in Candida albicans: (A) Principal component analysis of the entire transcriptome dataset of 6453 transcripts across 89 conditions. Samples are plotted by their first two principal components. The first letter of the sample name represents the treatment (C: De Man, Rogosa, and Sharpe medium [MRS] control, H: HCl, L: lactic, A: acetic, P: propionic, B: butyric acid), the middle number represents the time point (1: T1, 2: T2, 3: T3, 4: T4), whereas the last letter refers to the biological replicate (B, C, D, or F). (B) Hierarchical clustering of Gene Ontology (GO) Biological Process terms based on their enrichment in lists of genes differentially expressed in response to individual WOAs and individual time points. Before enrichment analysis, differentially expressed gene lists were removed of genes also significantly modulated in HCl-treated vs. untreated cells. The heat map is color-coded based on Bonferroni-corrected P values, as indicated by the color bar at the bottom. Only GO terms with an adjusted P value < 5 × 10−4 in at least one of the 16 conditions were included in the heat map. Related GO terms are color-coded based on the more general functional category indicated on the right. Distance metric: Euclidean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390566&req=5

fig2: Global transcriptome changes induced by weak organic acids (WOAs) in Candida albicans: (A) Principal component analysis of the entire transcriptome dataset of 6453 transcripts across 89 conditions. Samples are plotted by their first two principal components. The first letter of the sample name represents the treatment (C: De Man, Rogosa, and Sharpe medium [MRS] control, H: HCl, L: lactic, A: acetic, P: propionic, B: butyric acid), the middle number represents the time point (1: T1, 2: T2, 3: T3, 4: T4), whereas the last letter refers to the biological replicate (B, C, D, or F). (B) Hierarchical clustering of Gene Ontology (GO) Biological Process terms based on their enrichment in lists of genes differentially expressed in response to individual WOAs and individual time points. Before enrichment analysis, differentially expressed gene lists were removed of genes also significantly modulated in HCl-treated vs. untreated cells. The heat map is color-coded based on Bonferroni-corrected P values, as indicated by the color bar at the bottom. Only GO terms with an adjusted P value < 5 × 10−4 in at least one of the 16 conditions were included in the heat map. Related GO terms are color-coded based on the more general functional category indicated on the right. Distance metric: Euclidean.
Mentions: Unsupervised principal component analysis (Figure 2A) and hierarchical clustering (Figure S2) of the 89 analyzed samples led to the following observations. Consistent with the effect on the OD of the cultures (Figure 1B), the HCl-treated samples clustered more closely with the untreated samples than with any other samples, indicating that the effect exerted by WOAs on C. albicans goes beyond a mere response to acidification of the media. Lactic acid−treated samples formed a cluster by themselves that was relatively compact through time, suggesting a unique cellular response to this acid. Acetic acid−treated cells were closer to control cells at T1 but clustered away from all other samples at T3 and T4, indicating a distinct feature in the transcriptional response of C. albicans to this particular acid especially under chronic exposure. Also, propionic and butyric acid displayed a differential behavior between T1 and subsequent time points; however, they also were consistently more similar to each other than to any other treatment.

Bottom Line: Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations.Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels and of ribosomal RNA in particular.In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease.

View Article: PubMed Central - PubMed

Affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

Show MeSH
Related in: MedlinePlus