Functional specialization and differential regulation of short‐chain carboxylic acid transporters in the pathogen Candida albicans
Open accessAbstract
The major fungal pathogen Candida albicans has the metabolic flexibility to assimilate a wide range of nutrients in its human host. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources contributes to its virulence. JEN1 encodes a monocarboxylate transporter in C. albicans and we show that its paralogue, JEN2, encodes a novel dicarboxylate plasma membrane transporter, subjected to glucose repression. A strain deleted in both genes lost the ability to transport lactic, malic and succinic acids by a mediated mechanism and it displayed a growth defect on these substrates. Although no significant morphogenetic or virulence defects were found in the double mutant strain, both JEN1 and JEN2 were strongly induced during infection. Jen1-GFP (green fluorescent protein) and Jen2-GFP were upregulated following the phagocytosis of C. albicans cells by neutrophils and macrophages, displaying similar behaviour to an Icl1-GFP fusion. In the murine model of systemic candidiasis approximately 20-25% of C. albicans cells infecting the kidney expressed Jen1-GFP and Jen2-GFP. Our data suggest that Jen1 and Jen2 are expressed in glucose-poor niches within the host, and that these short-chain carboxylic acid transporters may be important in the early stages of infection.
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This hypothesis was supported by the apparent expression regulation of two C. albicans carboxylic acids transporter genes, JEN1 and JEN2, following macrophages internalization.
“This hypothesis was supported by the apparent expression regulation of two C. albicans carboxylic acids transporter genes, JEN1 and JEN2, following macrophages internalization.”
From Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate (2015) · cites this paper as Vieira et al., 2010
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- Authors
- Vieira, N., Casal, M., Johansson, B., MacCallum, D. M., Brown, A. J. P., & Paiva, S.
- Affiliations
- University of Minho (PT)
- University of Aberdeen (GB)
- Corresponding author
- Paiva, Sandra
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 75
- Issue
- 6
- Pages
- 1337-1354
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC2859246
- OpenAlex
- W1980561427
- Cited by
- 63
- References
- 80
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 4 · 2012: 5
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- Funders
- Wellcome Trust (080088)
- Biotechnology and Biological Sciences Research Council (BBS/B/06679, BB/C510391/1, BB/F00513X/1, BB/F010826/1)
- Fundação para a Ciência e a Tecnologia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, dicarboxylate transporter, monocarboxylate transporters, glucose repression, non-fermentable carbon sources, systemic candidiasis, host-pathogen interaction, neutrophil phagocytosis, macrophages, lactic acid, malic acid, succinic acid, virulence
- MeSH terms
- Animals, Candida albicans, Candidiasis, Carboxylic Acids, Fungal Proteins, Macrophages, Neutrophils, Phagocytosis, Recombinant Fusion Proteins, Survival Analysis, Gene Deletion, Genes, Reporter, Artificial Gene Fusion, Gene Expression Profiling, Membrane Transport Proteins, Green Fluorescent Proteins, Mice
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