Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
AI Summary:
This study profiled previously characterized and phenotypically distinct C. albicans bloodstream isolates. The study found a significant relationship between biofilm heterogeneity and azole resistance.AI Topics:
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.
Delaney, Christopher
Author
Ware, Alicia and Johnston, William and Delaney, Christopher and Butcher, Mark C. and Ramage, Gordon and Price, Lesley and Butcher, John and Kean, Ryan (2025) Dry surface biofilm formation by Candida auris facilitates persistence and tolerance to sodium hypochlorite. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70022. ISSN 0903-4641
Alshehri, Muhanna and Alqahtani, Saeed and Murali, Pranitha and Delaney, Christopher and Johnston, William and Brown, Jason L. (2025) Organotypic tissue model systems for investigating host-pathogen interactions in vitro. Journal of Visualized Experiments, 28 (217): e67487. ISSN 1940-087X
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
See full publications listShort, Bryn
Author
Allkja, Jontana and Bakri, Ahmed and Short, Bryn and Gilmour, Andrew and Brown, Jason L. and Bal, Abhijit M. and Newby, Kelly J.M. and Jenkins, Toby and Short, Rob D. and Williams, Craig and Ramage, Gordon (2025) Investigating the prevalence of fungi in diabetic ulcers: an under-recognised contributor to polymicrobial biofilms. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70025. ISSN 0903-4641
Abduljalil, Hafsa and Alshanta, Om Alkhir and Chougule, Safa and Butcher, Mark and Short, Bryn and Mclean, William and Parry, Neil and O'Keeffe, Joanne and Ramage, Gordon (2025) Lactams exhibit potent antifungal activity against monospecies and multispecies interkingdom biofilms on a novel hydrogel skin model. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (1): e13510. ISSN 0903-4641
Jatkowska, Aleksandra and Gkikas, Konstantinos and Nichols, Ben and Short, Bryn and Rizou, Vasiliki-Konstantina and Kapranos, Panagiotis and Klein Gunnewiek, Jennier and Christina, Edelyn and Svolos, Vaios and Quince, Christopher and Gerasimidis, Konstantinos (2024) Dose-dependent effects of enteral nutrition on the faecal microbiota and short chain fatty acids. Clinical Nutrition, 43 (5). pp. 1200-1207. ISSN 0261-5614
See full publications listRajendran, Ranjith
Author
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
See full publications listKean, Ryan
Author
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
Johnston, William and Ware, Alicia and Kuiters, Willemijn Frederique and Delaney, Christopher and Brown, Jason Lee and Hagen, Suzanne and Corcoran, David and Cummings, Matthew and Ramage, Gordon and Kean, Ryan (2023) In vitro bacterial vaginosis biofilm community manipulation using endolysin therapy. Biofilm, 5: 100101. ISSN 2590-2075
See full publications listBurgess, Karl
Author
Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
See full publications listWilliams, Craig
Author
Allkja, Jontana and Bakri, Ahmed and Short, Bryn and Gilmour, Andrew and Brown, Jason L. and Bal, Abhijit M. and Newby, Kelly J.M. and Jenkins, Toby and Short, Rob D. and Williams, Craig and Ramage, Gordon (2025) Investigating the prevalence of fungi in diabetic ulcers: an under-recognised contributor to polymicrobial biofilms. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70025. ISSN 0903-4641
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
Ramage, Gordon and Borghi, Elisa and Fortuna Rodrigues, Celia and Kean, Ryan and Williams, Craig and Lopez-Ribot, Jose (2023) Our current clinical understanding of Candida biofilms: where are we two decades on? APMIS: Journal of Pathology, Microbiology and Immunology, 131 (11). pp. 636-653. ISSN 0903-4641
See full publications listMunro, Carol A.
Author
Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075
See full publications listRamage, Gordon
Author
Allkja, Jontana and Bakri, Ahmed and Short, Bryn and Gilmour, Andrew and Brown, Jason L. and Bal, Abhijit M. and Newby, Kelly J.M. and Jenkins, Toby and Short, Rob D. and Williams, Craig and Ramage, Gordon (2025) Investigating the prevalence of fungi in diabetic ulcers: an under-recognised contributor to polymicrobial biofilms. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70025. ISSN 0903-4641
Ware, Alicia and Johnston, William and Delaney, Christopher and Butcher, Mark C. and Ramage, Gordon and Price, Lesley and Butcher, John and Kean, Ryan (2025) Dry surface biofilm formation by Candida auris facilitates persistence and tolerance to sodium hypochlorite. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70022. ISSN 0903-4641
Abduljalil, Hafsa and Alshanta, Om Alkhir and Chougule, Safa and Butcher, Mark and Short, Bryn and Mclean, William and Parry, Neil and O'Keeffe, Joanne and Ramage, Gordon (2025) Lactams exhibit potent antifungal activity against monospecies and multispecies interkingdom biofilms on a novel hydrogel skin model. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (1): e13510. ISSN 0903-4641
See full publications listAvailable under License Creative Commons Attribution.
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