An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype

Biofilm · 8 authors, 5 centres

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TL;DR

It found a significant relationship between biofilm heterogeneity and azole resistance, and identified shared metabolic responses to serum, notably the arachidonic acid cascade.

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Researchers assessed antifungal susceptibility, biofilm formation, and morphological changes. They employed RNA-Seq and LC-MS to map transcriptional and metabolic reprogramming in response to serum. The central finding was a significant relationship between biofilm heterogeneity and azole resistance (P < 0.05). Low biofilm forming isolates showed increased biofilm and hyphal elongation in serum. Transcriptional responses were distinct between low and high biofilm forming strains, indicating plasticity in stress responses. Metabolic responses shared common pathways, including a high upregulation of the arachidonic acid cascade, which induced biofilm formation 3-fold in low biofilm forming strains.

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other

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infectious disease

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100% · A

ORIGINAL PAPER

PMC10034394

An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype

Biofilm

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ABSTRACT

Candida albicans is the most prevalent and notorious of the Candida species involved in bloodstream infections, which is characterised by its capacity to form robust biofilms. Biofilm formation is an important clinical entity shown to be highly variable among clinical isolates. There are various environmental and physiological factors, including nutrient availability which influence the phenotype of Candida species. However, mechanisms underpinning adaptive biofilm heterogeneity have not yet been fully explored. Within this study we have profiled previously characterised and phenotypically distinct C. albicans bloodstream isolates. We assessed the dynamic susceptibility of these differing populations to antifungal treatments using population analysis profiling in addition to assessing biofilm formation and morphological changes. High throughput methodologies of RNA-Seq and LC-MS were employed to map and integrate the transcriptional and metabolic reprogramming undertaken by heterogenous C. albicans isolates in response to biofilm and hyphal inducing serum. We found a significant relationship between biofilm heterogeneity and azole resistance (P < 0.05). In addition, we observed that in response to serum our low biofilm forming (LBF) C. albicans exhibited a significant increase in biofilm formation and hyphal elongation. The transcriptional reprogramming of LBF strains compared to high biofilm forming (HBF) was distinct, indicating a high level of plasticity and variation in stress responses by heterogenous strains. The metabolic responses, although variable between LBF and HBF, shared many of the same responses to serum. Notably, a high upregulation of the arachidonic acid cascade, part of the COX pathway, was observed and this pathway was found to induce biofilm formation in LBF 3-fold. C. albicans is a highly heterogenous bloodstream pathogen with clinical isolates varying in antifungal tolerance and biofilm formation. In addition to this, C. albicans is capable of highly complex and variable regulation of transcription and metabolic pathways and heterogeneity across isolates further increases the complexity of these pathways. Here we have shown with a dual and integrated approach, the importance of studying a diverse panel of C. albicans isolates, which has the potential to reveal distinct pathways that can harnessed for drug discovery.

CITATION EXPORT

Christopher Delaney, Bryn Short, Ranjith Rajendran et al.. An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm. (2023). https://doi.org/10.1016/j.bioflm.2023.100112

AUTHORS

8 · 5 CENTRES

Christopher Delaney, Bryn Short, Ranjith Rajendran, Ryan Kean, Karl Burgess, Craig Williams, Carol A. Munro, Gordon Ramage

aSchool of Medicine, College of Medical, Veterinary and Life Sciences (MVLS), University of Glasgow, UK
bDepartment of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
cInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Max Born Crescent, Edinburgh, UK
dMicrobiology Department, Lancaster Royal Infirmary, University of Lancaster, Lancaster, UK
eSchool of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, UK