Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping

Rajendran, R. et al. (2016) Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping. Scientific Reports, 6, 35436. (doi: 10.1038/srep35436) (PMID:27765942) (PMCID:PMC5073228)

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.

• Item Type: Articles
• Additional Information: This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Burgess, Dr Karl and Kean, Mr Ryan and Ramage, Professor Gordon and Rajendran, Dr Ranjith and Sherry, Dr Leighann and Jones, Dr Brian
• Authors: Rajendran, R., May, A., Sherry, L., Kean, R., Williams, C., Jones, B. L., Burgess, K., Heringa, J., Abeln, S., Brandt, B. W., Munro, C. A., and Ramage, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Scientific Reports 6: 35436
• Publisher Policy: Reproduced under a Creative Commons License