Dataset Information

Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence.

ABSTRACT: Candida albicans contains four ORFs (GIT1,2,3,4) predicted to encode proteins involved in the transport of glycerophosphodiester metabolites. Previously, we reported that Git1, encoded by ORF 19.34, is responsible for the transport of intact glycerophosphoinositol but not glycerophosphocholine (GroPCho). Here, we report that a strain lacking both GIT3 (ORF 19.1979) and GIT4 (ORF 19.1980) is unable to transport [(3)H]GroPCho into the cell. In the absence of a GroPCho transporter, C. albicans can utilize GroPCho via a mechanism involving extracellular hydrolysis. Upon reintegration of either GIT3 or GIT4 into the genome, measurable uptake of [(3)H]GroPCho is observed. Transport assays and kinetic analyses indicate that Git3 has the greater transport velocity. We present evidence that GDE1 (ORF 19.3936) codes for an enzyme with glycerophosphodiesterase activity against GroPCho. Homozygous deletion of GDE1 results in a buildup of internal GroPCho that is restored to wild type levels by reintegration of GDE1 into the genome. The transcriptional regulator, Pho4, is shown to regulate the expression of GIT3, GIT4, and GDE1. Finally, Git3 is shown to be required for full virulence in a mouse model of disseminated candidiasis, and Git3 sequence orthologs are present in other pathogenic Candida species. In summary, we have characterized multiple aspects of GroPCho utilization by C. albicans and have demonstrated that GroPCho transport plays a key role in the growth of the organism in the host.

SUBMITTER: Bishop AC

PROVIDER: S-EPMC3837134 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

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Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence.

Bishop Andrew C AC Ganguly Shantanu S Solis Norma V NV Cooley Benjamin M BM Jensen-Seaman Michael I MI Filler Scott G SG Mitchell Aaron P AP Patton-Vogt Jana J

The Journal of biological chemistry 20131010 47

Candida albicans contains four ORFs (GIT1,2,3,4) predicted to encode proteins involved in the transport of glycerophosphodiester metabolites. Previously, we reported that Git1, encoded by ORF 19.34, is responsible for the transport of intact glycerophosphoinositol but not glycerophosphocholine (GroPCho). Here, we report that a strain lacking both GIT3 (ORF 19.1979) and GIT4 (ORF 19.1980) is unable to transport [(3)H]GroPCho into the cell. In the absence of a GroPCho transporter, C. albicans can ...[more]

PMID: 24114876

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Project description:UnlabelledCandida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodates C. albicans as part of the normal microbiota, where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, rendering C. albicans impaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulate C. albicans physiology, and we hypothesize that they are key environmental signals for retaining C. albicans in the host-compatible, commensal state.ImportanceThe yeast Candida albicans causes both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However, C. albicans is not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection by C. albicans are coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes of C. albicans at the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressing C. albicans infections.

Dataset Information

Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence.

Publications

Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence.

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