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Candida albicans exhibits enhanced alkaline and temperature induction of Efg1-regulated transcripts relative to Candida dubliniensis.

Caplice N, Moran GP - Genom Data (2015)

Bottom Line: Filamentous growth is an important virulence trait of the human pathogenic fungi within the genus Candida, and the greater propensity of C. albicans to form hyphae has been proposed to account for the greater virulence of this species relative to the less pathogenic species C. dubliniensis.We could identify conserved core temperature and pH responses, however many signature Efg1-regulated, hypha-induced transcripts (e.g. ECE1, HWP1) exhibited reduced or lack of induction in C. dubliniensis.Comparison of the activity of the HWP1 and ECE1 promoters in both species using GFP fusions showed a lag in serum induced fluorescence in C. dubliniensis relative to C. albicans and nutrient depletion was required for maximal expression of these Efg1-regulated transcripts in C. dubliniensis.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Dublin 2, Ireland.

ABSTRACT
Filamentous growth is an important virulence trait of the human pathogenic fungi within the genus Candida, and the greater propensity of C. albicans to form hyphae has been proposed to account for the greater virulence of this species relative to the less pathogenic species C. dubliniensis. In this meta-analysis, we compare the transcriptional response of C. dubliniensis and C. albicans to the individual environmental stimuli that shape the gene expression profiles during filamentation in 10% serum, namely alkaline pH, 37 °C and reduced cell density. We could identify conserved core temperature and pH responses, however many signature Efg1-regulated, hypha-induced transcripts (e.g. ECE1, HWP1) exhibited reduced or lack of induction in C. dubliniensis. Comparison of the activity of the HWP1 and ECE1 promoters in both species using GFP fusions showed a lag in serum induced fluorescence in C. dubliniensis relative to C. albicans and nutrient depletion was required for maximal expression of these Efg1-regulated transcripts in C. dubliniensis.

No MeSH data available.


Related in: MedlinePlus

A comparison of the transcriptional responses of C. albicans (Ca) and C. dubliniensis (Cd) to dilution at 30 °C and 37 °C. The ‘heat-map’ on the left shows the expression patterns for 419 genes identified as > 2-fold regulated (t-test p < 0.05) in C. albicans following a switch to 37 °C (from (10). Expression following dilution to medium at 30 °C is also shown. On the right, the expression of the orthologous gene in C. dubliniensis under similar conditions is shown. Expression refers to fold-change relative to the preculture conditions (30 °C) and is denoted by the colour according to the legend. Certain sections are expanded in panels (a), (b) and (c) for clarity, as detailed in the text.
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f0015: A comparison of the transcriptional responses of C. albicans (Ca) and C. dubliniensis (Cd) to dilution at 30 °C and 37 °C. The ‘heat-map’ on the left shows the expression patterns for 419 genes identified as > 2-fold regulated (t-test p < 0.05) in C. albicans following a switch to 37 °C (from (10). Expression following dilution to medium at 30 °C is also shown. On the right, the expression of the orthologous gene in C. dubliniensis under similar conditions is shown. Expression refers to fold-change relative to the preculture conditions (30 °C) and is denoted by the colour according to the legend. Certain sections are expanded in panels (a), (b) and (c) for clarity, as detailed in the text.

Mentions: Analysis of the data set of Kadosh and Johnson showed that following a switch to 37 °C, C. albicans mounted a transcriptional response consisting of 419 genes whose expression was regulated > 2-fold (t-test p < 0.05). The list of temperature-induced genes (223 genes) was enriched for genes involved in ribosome biogenesis (39 genes), amino acid biosynthesis (15 genes) and lipid biosynthesis (18 genes). When the effects of cell density and temperature shifts on global gene expression were investigated in C. dubliniensis, it was revealed that this response was largely conserved in and is likely a response to inoculation in fresh nutrient rich media (Fig. 3). However, our analysis identified a specific response in C. albicans that included several genes normally associated with filamentation at 37 °C. As previously reported, temperature shifts to 37 °C induced expression of ECE1 and HWP1 in C. albicans[24], [25]. Indeed, even in the absence of a temperature shift, a change in cell density was sufficient to induce expression of ECE1 and HWP1 in C. albicans[24]. In C. dubliniensis, the orthologues of ECE1 and HWP1 exhibited weak (< 2-fold) or no induction in response to 37 °C, respectively (Fig. 3a). An additional cluster of C. albicans highly induced genes exhibited down-regulation in C. dubliniensis, including the C. dubliniensis orthologue of EED1, an activator of UME6 expression (Fig. 3b). Additional genes encoding factors with roles in the cell cycle (CCN1, GIN4) cytoskeleton organisation (CDC12, ARF3, CCT3, TCP2), maintenance of hyphal growth (CLA4) and DNA replication (POL30, CDC47) that were induced > 2-fold in C. albicans at 37 °C exhibited no induction in C. dubliniensis (Fig. 3c). Like ECE1 and HWP1, the majority of these temperature (37 °C) induced genes in C. albicans also exhibited induction following culture dilution at 30 °C (e.g. EED1, CLA4, RNR1; Fig. 3). The similarity of the species-specific response of C. albicans to culture dilution and the shift to 37 °C is likely due to the similar affects of these stimuli on the cAMP-PKA pathway. Culture dilution is thought to remove farnesol-mediated repression of the cAMP-PKA pathway, perhaps at the level of adenylate cyclase [24]. Temperature shifts are thought to act by relieving Hsp90 mediated repression of the cAMP-PKA pathway [12]. However, the level of induction was generally highest following the temperature shift, indicating that either this stimulus has a stronger effect on the cAMP-PKA pathway or that the effects of dilution and temperature are cumulative.


Candida albicans exhibits enhanced alkaline and temperature induction of Efg1-regulated transcripts relative to Candida dubliniensis.

Caplice N, Moran GP - Genom Data (2015)

A comparison of the transcriptional responses of C. albicans (Ca) and C. dubliniensis (Cd) to dilution at 30 °C and 37 °C. The ‘heat-map’ on the left shows the expression patterns for 419 genes identified as > 2-fold regulated (t-test p < 0.05) in C. albicans following a switch to 37 °C (from (10). Expression following dilution to medium at 30 °C is also shown. On the right, the expression of the orthologous gene in C. dubliniensis under similar conditions is shown. Expression refers to fold-change relative to the preculture conditions (30 °C) and is denoted by the colour according to the legend. Certain sections are expanded in panels (a), (b) and (c) for clarity, as detailed in the text.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664712&req=5

f0015: A comparison of the transcriptional responses of C. albicans (Ca) and C. dubliniensis (Cd) to dilution at 30 °C and 37 °C. The ‘heat-map’ on the left shows the expression patterns for 419 genes identified as > 2-fold regulated (t-test p < 0.05) in C. albicans following a switch to 37 °C (from (10). Expression following dilution to medium at 30 °C is also shown. On the right, the expression of the orthologous gene in C. dubliniensis under similar conditions is shown. Expression refers to fold-change relative to the preculture conditions (30 °C) and is denoted by the colour according to the legend. Certain sections are expanded in panels (a), (b) and (c) for clarity, as detailed in the text.
Mentions: Analysis of the data set of Kadosh and Johnson showed that following a switch to 37 °C, C. albicans mounted a transcriptional response consisting of 419 genes whose expression was regulated > 2-fold (t-test p < 0.05). The list of temperature-induced genes (223 genes) was enriched for genes involved in ribosome biogenesis (39 genes), amino acid biosynthesis (15 genes) and lipid biosynthesis (18 genes). When the effects of cell density and temperature shifts on global gene expression were investigated in C. dubliniensis, it was revealed that this response was largely conserved in and is likely a response to inoculation in fresh nutrient rich media (Fig. 3). However, our analysis identified a specific response in C. albicans that included several genes normally associated with filamentation at 37 °C. As previously reported, temperature shifts to 37 °C induced expression of ECE1 and HWP1 in C. albicans[24], [25]. Indeed, even in the absence of a temperature shift, a change in cell density was sufficient to induce expression of ECE1 and HWP1 in C. albicans[24]. In C. dubliniensis, the orthologues of ECE1 and HWP1 exhibited weak (< 2-fold) or no induction in response to 37 °C, respectively (Fig. 3a). An additional cluster of C. albicans highly induced genes exhibited down-regulation in C. dubliniensis, including the C. dubliniensis orthologue of EED1, an activator of UME6 expression (Fig. 3b). Additional genes encoding factors with roles in the cell cycle (CCN1, GIN4) cytoskeleton organisation (CDC12, ARF3, CCT3, TCP2), maintenance of hyphal growth (CLA4) and DNA replication (POL30, CDC47) that were induced > 2-fold in C. albicans at 37 °C exhibited no induction in C. dubliniensis (Fig. 3c). Like ECE1 and HWP1, the majority of these temperature (37 °C) induced genes in C. albicans also exhibited induction following culture dilution at 30 °C (e.g. EED1, CLA4, RNR1; Fig. 3). The similarity of the species-specific response of C. albicans to culture dilution and the shift to 37 °C is likely due to the similar affects of these stimuli on the cAMP-PKA pathway. Culture dilution is thought to remove farnesol-mediated repression of the cAMP-PKA pathway, perhaps at the level of adenylate cyclase [24]. Temperature shifts are thought to act by relieving Hsp90 mediated repression of the cAMP-PKA pathway [12]. However, the level of induction was generally highest following the temperature shift, indicating that either this stimulus has a stronger effect on the cAMP-PKA pathway or that the effects of dilution and temperature are cumulative.

Bottom Line: Filamentous growth is an important virulence trait of the human pathogenic fungi within the genus Candida, and the greater propensity of C. albicans to form hyphae has been proposed to account for the greater virulence of this species relative to the less pathogenic species C. dubliniensis.We could identify conserved core temperature and pH responses, however many signature Efg1-regulated, hypha-induced transcripts (e.g. ECE1, HWP1) exhibited reduced or lack of induction in C. dubliniensis.Comparison of the activity of the HWP1 and ECE1 promoters in both species using GFP fusions showed a lag in serum induced fluorescence in C. dubliniensis relative to C. albicans and nutrient depletion was required for maximal expression of these Efg1-regulated transcripts in C. dubliniensis.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Dublin 2, Ireland.

ABSTRACT
Filamentous growth is an important virulence trait of the human pathogenic fungi within the genus Candida, and the greater propensity of C. albicans to form hyphae has been proposed to account for the greater virulence of this species relative to the less pathogenic species C. dubliniensis. In this meta-analysis, we compare the transcriptional response of C. dubliniensis and C. albicans to the individual environmental stimuli that shape the gene expression profiles during filamentation in 10% serum, namely alkaline pH, 37 °C and reduced cell density. We could identify conserved core temperature and pH responses, however many signature Efg1-regulated, hypha-induced transcripts (e.g. ECE1, HWP1) exhibited reduced or lack of induction in C. dubliniensis. Comparison of the activity of the HWP1 and ECE1 promoters in both species using GFP fusions showed a lag in serum induced fluorescence in C. dubliniensis relative to C. albicans and nutrient depletion was required for maximal expression of these Efg1-regulated transcripts in C. dubliniensis.

No MeSH data available.


Related in: MedlinePlus