Functional specialization and differential regulation of short-chain carboxylic acid transporters in the pathogen Candida albicans.
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.
Vieira
Neide
N
Department of Biology, Molecular and Environmental Biology Centre (CBMA), University of Minho, Braga, Portugal.
Casal
Margarida
M
Johansson
Björn
B
MacCallum
Donna M
DM
Brown
Alistair J P
AJ
Paiva
Sandra
S
D000818:Animals; D019677:Artificial Gene Fusion; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development; D002177:Candidiasis / Q000382:microbiology; D002264:Carboxylic Acids / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000382:microbiology; D010587:Phagocytosis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016019:Survival Analysis
D002264:Carboxylic Acids; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins