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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.


(a) Venn diagram showing the similarity of the alkaline induced response (≥ 2-fold) in C. dubliniensis and C. albicans from Bensen et al. [3]. (b) Position-specific probability matrix generated with MEME showing the motif identified in the promoters of pH-regulated genes in C. dubliniensis. The probability of each nucleotide appearing at each position corresponds to the height of each individual letter at that position multiplied by the total height of the ‘stack’ at that position. (c) Cartoon showing the relative position and frequency of the motif in the promoters of pH-regulated genes identified by ANOVA (see text). The line represents the promoter length (up to − 2000 bases or to the next chromosomal feature) relative to the respective ORF (not to scale). Black triangles represent to location of motifs with a 5′ ‘CC’ and grey triangles those with a 5′ ‘CA’. Triangles on top of the line indicate motifs on the sense strand, lower symbols indicate antisense motifs. Exact positions of motifs are given in Table S1.
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f0010: (a) Venn diagram showing the similarity of the alkaline induced response (≥ 2-fold) in C. dubliniensis and C. albicans from Bensen et al. [3]. (b) Position-specific probability matrix generated with MEME showing the motif identified in the promoters of pH-regulated genes in C. dubliniensis. The probability of each nucleotide appearing at each position corresponds to the height of each individual letter at that position multiplied by the total height of the ‘stack’ at that position. (c) Cartoon showing the relative position and frequency of the motif in the promoters of pH-regulated genes identified by ANOVA (see text). The line represents the promoter length (up to − 2000 bases or to the next chromosomal feature) relative to the respective ORF (not to scale). Black triangles represent to location of motifs with a 5′ ‘CC’ and grey triangles those with a 5′ ‘CA’. Triangles on top of the line indicate motifs on the sense strand, lower symbols indicate antisense motifs. Exact positions of motifs are given in Table S1.

Mentions: As the above data indicated that the alkaline pH shift plays an important role in inducing filamentation in C. dubliniensis, we analysed the transcriptional response of C. dubliniensis following a transition from acidic to alkaline pH. A total of 425 genes exhibited 2-fold up-regulation during a shift from pH 4.5 to 7.2 in Lee's medium (t-test p < 0.05). This group included genes associated with the cell surface (orthologues of PHR1, EAP1, IFF11, SUN41), metal ion transport (orthologues of CFL11, CFL4, ENA22, PHO84, PHO89) filamentous growth (orthologues of SFL1, UME6, RAS1, RFG1, TEC1) and amino acid metabolism (orthologues of ARO4, HIS3, SAM4). We observed strong conservation between the pH responses of C. albicans and C. dubliniensis, with 81 of the C. albicans alkaline up regulated genes described by Bensen et al. up regulated at least 2-fold in C. dubliniensis (t-test p < 0.05) at pH 7.2. (Fig. 2a) [23]. This group included many of the signature pH responsive genes such as PHR1, ENA22, RIM101 and several ferric reductases (Table S1). However, unlike C. albicans, significant (i.e. > 2-fold) induction of the orthologues of the Efg1-regulated genes EED1, SAP6, ECE1 and HWP1 was not observed at alkaline pH in C. dubliniensis. C. albicans also exhibited approximately 10-fold higher levels of induction of the Efg1-regulated transcripts CSA1 and RBT1.


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

Caplice N, Moran GP - Genom Data (2015)

(a) Venn diagram showing the similarity of the alkaline induced response (≥ 2-fold) in C. dubliniensis and C. albicans from Bensen et al. [3]. (b) Position-specific probability matrix generated with MEME showing the motif identified in the promoters of pH-regulated genes in C. dubliniensis. The probability of each nucleotide appearing at each position corresponds to the height of each individual letter at that position multiplied by the total height of the ‘stack’ at that position. (c) Cartoon showing the relative position and frequency of the motif in the promoters of pH-regulated genes identified by ANOVA (see text). The line represents the promoter length (up to − 2000 bases or to the next chromosomal feature) relative to the respective ORF (not to scale). Black triangles represent to location of motifs with a 5′ ‘CC’ and grey triangles those with a 5′ ‘CA’. Triangles on top of the line indicate motifs on the sense strand, lower symbols indicate antisense motifs. Exact positions of motifs are given in Table S1.
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Related In: Results  -  Collection

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f0010: (a) Venn diagram showing the similarity of the alkaline induced response (≥ 2-fold) in C. dubliniensis and C. albicans from Bensen et al. [3]. (b) Position-specific probability matrix generated with MEME showing the motif identified in the promoters of pH-regulated genes in C. dubliniensis. The probability of each nucleotide appearing at each position corresponds to the height of each individual letter at that position multiplied by the total height of the ‘stack’ at that position. (c) Cartoon showing the relative position and frequency of the motif in the promoters of pH-regulated genes identified by ANOVA (see text). The line represents the promoter length (up to − 2000 bases or to the next chromosomal feature) relative to the respective ORF (not to scale). Black triangles represent to location of motifs with a 5′ ‘CC’ and grey triangles those with a 5′ ‘CA’. Triangles on top of the line indicate motifs on the sense strand, lower symbols indicate antisense motifs. Exact positions of motifs are given in Table S1.
Mentions: As the above data indicated that the alkaline pH shift plays an important role in inducing filamentation in C. dubliniensis, we analysed the transcriptional response of C. dubliniensis following a transition from acidic to alkaline pH. A total of 425 genes exhibited 2-fold up-regulation during a shift from pH 4.5 to 7.2 in Lee's medium (t-test p < 0.05). This group included genes associated with the cell surface (orthologues of PHR1, EAP1, IFF11, SUN41), metal ion transport (orthologues of CFL11, CFL4, ENA22, PHO84, PHO89) filamentous growth (orthologues of SFL1, UME6, RAS1, RFG1, TEC1) and amino acid metabolism (orthologues of ARO4, HIS3, SAM4). We observed strong conservation between the pH responses of C. albicans and C. dubliniensis, with 81 of the C. albicans alkaline up regulated genes described by Bensen et al. up regulated at least 2-fold in C. dubliniensis (t-test p < 0.05) at pH 7.2. (Fig. 2a) [23]. This group included many of the signature pH responsive genes such as PHR1, ENA22, RIM101 and several ferric reductases (Table S1). However, unlike C. albicans, significant (i.e. > 2-fold) induction of the orthologues of the Efg1-regulated genes EED1, SAP6, ECE1 and HWP1 was not observed at alkaline pH in C. dubliniensis. C. albicans also exhibited approximately 10-fold higher levels of induction of the Efg1-regulated transcripts CSA1 and RBT1.

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.