Functional specialization and differential regulation of short-chain carboxylic acid transporters in the pathogen Candida albicans

Neide Vieira, Margarida Casal, Björn Johansson, Donna M MacCallum, Alistair J P Brown, Sandra Paiva

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Abstract

Summary 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.

Original languageEnglish
Pages (from-to)1337-1354
Number of pages18
JournalMolecular Microbiology
Volume75
Issue number6
Early online date4 Dec 2009
DOIs
Publication statusPublished - Mar 2010

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Carboxylic Acids
Candida albicans
Aptitude
Glucose
Virulence
Succinates
Infection
Membrane Transport Proteins
Green Fluorescent Proteins
Phagocytosis
Milk
Neutrophils
Carbon
Macrophages
Cell Membrane
Kidney
Food
Growth
Genes

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Functional specialization and differential regulation of short-chain carboxylic acid transporters in the pathogen Candida albicans. / Vieira, Neide; Casal, Margarida; Johansson, Björn; MacCallum, Donna M; Brown, Alistair J P; Paiva, Sandra.

In: Molecular Microbiology, Vol. 75, No. 6, 03.2010, p. 1337-1354.

Research output: Contribution to journalArticle

Vieira, Neide ; Casal, Margarida ; Johansson, Björn ; MacCallum, Donna M ; Brown, Alistair J P ; Paiva, Sandra. / Functional specialization and differential regulation of short-chain carboxylic acid transporters in the pathogen Candida albicans. In: Molecular Microbiology. 2010 ; Vol. 75, No. 6. pp. 1337-1354.
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