Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping

Ranjith Rajendran, Ali May, Leighann Sherry, Ryan Kean, Craig Williams, Brian L. Jones, Karl V Burgess, Jaap Heringa, Sanne Abeln, Bernd W. Brandt, Carol A. Munro, Gordon Ramage

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Abstract

Candida albicans biofilm formation is an important virulence factor in the pathogenesis of disease, a characteristic which has been shown to be heterogeneous in clinical isolates. Using an unbiased computational approach we investigated the central metabolic pathways driving biofilm heterogeneity. Transcripts from high (HBF) and low (LBF) biofilm forming isolates were analysed by RNA sequencing, with 6312 genes identified to be expressed in these two phenotypes. With a dedicated computational approach we identified and validated a significantly differentially expressed subnetwork of genes associated with these biofilm phenotypes. Our analysis revealed amino acid metabolism, such as arginine, proline, aspartate and glutamate metabolism, were predominantly upregulated in the HBF phenotype. On the contrary, purine, starch and sucrose metabolism was generally upregulated in the LBF phenotype. The aspartate aminotransferase gene AAT1 was found to be a common member of these amino acid pathways and significantly upregulated in the HBF phenotype. Pharmacological inhibition of AAT1 enzyme activity significantly reduced biofilm formation in a dose-dependent manner. Collectively, these findings provide evidence that biofilm phenotype is associated with differential regulation of metabolic pathways. Understanding and targeting such pathways, such as amino acid metabolism, is potentially useful for developing diagnostics and new antifungals to treat biofilm-based infections.
Original languageEnglish
Article number35436
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 21 Oct 2016

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Biofilms
Candida albicans
Transcriptome
Phenotype
Metabolic Networks and Pathways
arginine glutamate
Amino Acids
Genes
RNA Sequence Analysis
Virulence Factors
Aspartate Aminotransferases
Proline
Starch
Sucrose
Pharmacology
Enzymes
Infection

Cite this

Rajendran, R., May, A., Sherry, L., Kean, R., Williams, C., Jones, B. L., ... Ramage, G. (2016). Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping. Scientific Reports, 6, [35436 ]. https://doi.org/10.1038/srep35436

Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping. / Rajendran, Ranjith; May, Ali; Sherry, Leighann; Kean, Ryan ; Williams, Craig; Jones, Brian L.; Burgess, Karl V; Heringa, Jaap; Abeln, Sanne; Brandt, Bernd W.; Munro, Carol A.; Ramage, Gordon.

In: Scientific Reports, Vol. 6, 35436 , 21.10.2016.

Research output: Contribution to journalArticle

Rajendran, R, May, A, Sherry, L, Kean, R, Williams, C, Jones, BL, Burgess, KV, Heringa, J, Abeln, S, Brandt, BW, Munro, CA & Ramage, G 2016, 'Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping', Scientific Reports, vol. 6, 35436 . https://doi.org/10.1038/srep35436
Rajendran, Ranjith ; May, Ali ; Sherry, Leighann ; Kean, Ryan ; Williams, Craig ; Jones, Brian L. ; Burgess, Karl V ; Heringa, Jaap ; Abeln, Sanne ; Brandt, Bernd W. ; Munro, Carol A. ; Ramage, Gordon. / Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "Candida albicans biofilm formation is an important virulence factor in the pathogenesis of disease, a characteristic which has been shown to be heterogeneous in clinical isolates. Using an unbiased computational approach we investigated the central metabolic pathways driving biofilm heterogeneity. Transcripts from high (HBF) and low (LBF) biofilm forming isolates were analysed by RNA sequencing, with 6312 genes identified to be expressed in these two phenotypes. With a dedicated computational approach we identified and validated a significantly differentially expressed subnetwork of genes associated with these biofilm phenotypes. Our analysis revealed amino acid metabolism, such as arginine, proline, aspartate and glutamate metabolism, were predominantly upregulated in the HBF phenotype. On the contrary, purine, starch and sucrose metabolism was generally upregulated in the LBF phenotype. The aspartate aminotransferase gene AAT1 was found to be a common member of these amino acid pathways and significantly upregulated in the HBF phenotype. Pharmacological inhibition of AAT1 enzyme activity significantly reduced biofilm formation in a dose-dependent manner. Collectively, these findings provide evidence that biofilm phenotype is associated with differential regulation of metabolic pathways. Understanding and targeting such pathways, such as amino acid metabolism, is potentially useful for developing diagnostics and new antifungals to treat biofilm-based infections.",
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