Dataset Information

Candida albicans and Candida glabrata triosephosphate isomerase - a moonlighting protein that can be exposed on the candidal cell surface and bind to human extracellular matrix proteins.

ABSTRACT:

Background

Triosephosphate isomerase (Tpi1) is a glycolytic enzyme that has recently been reported also to be an atypical proteinaceous component of the Candida yeast cell wall. Similar to other known candidal "moonlighting proteins", surface-exposed Tpi1 is likely to contribute to fungal adhesion during the colonization and infection of a human host. The aim of our present study was to directly prove the presence of Tpi1 on C. albicans and C. glabrata cells under various growth conditions and characterize the interactions of native Tpi1, isolated and purified from the candidal cell wall, with human extracellular matrix proteins.

Results

Surface plasmon resonance measurements were used to determine the dissociation constants for the complexes of Tpi1 with host proteins and these values were found to fall within a relatively narrow range of 10^- 8-10^- 7 M. Using a chemical cross-linking method, two motifs of the Tpi1 molecule (aa 4-17 and aa 224-247) were identified to be directly involved in the interaction with vitronectin. A proposed structural model for Tpi1 confirmed that these interaction sites were at a considerable distance from the catalytic active site. Synthetic peptides with these sequences significantly inhibited Tpi1 binding to several extracellular matrix proteins suggesting that a common region on the surface of Tpi1 molecule is involved in the interactions with the host proteins.

Conclusions

The current study provided structural insights into the interactions of human extracellular matrix proteins with Tpi1 that can occur at the cell surface of Candida yeasts and contribute to the host infection by these fungal pathogens.

SUBMITTER: Satala D

PROVIDER: S-EPMC8252264 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Candida species, such as Candida albicans and Candida glabrata, cause infections at different host sites because they adapt their metabolism depending on the available nutrients. They are able to proliferate under both nutrient-rich and nutrient-poor conditions. This adaptation is what makes these fungi successful pathogens. For both species, sugars are very important nutrients and as the sugar level differs depending on the host niche, different sugar sensing systems must be present. Saccharomyces cerevisiae has been used as a model for the identification of these sugar sensing systems. One of the main carbon sources for yeast is glucose, for which three different pathways have been described. First, two transporter-like proteins, ScSnf3 and ScRgt2, sense glucose levels resulting in the induction of different hexose transporter genes. This situation is comparable in C. albicans and C. glabrata, where sensing of glucose by CaHgt4 and CgSnf3, respectively, also results in hexose transporter gene induction. The second glucose sensing mechanism in S. cerevisiae is via the G-protein coupled receptor ScGpr1, which causes the activation of the cAMP/PKA pathway, resulting in rapid adaptation to the presence of glucose. The main components of this glucose sensing system are also conserved in C. albicans and C. glabrata. However, it seems that the ligand(s) for CaGpr1 are not sugars but lactate and methionine. In C. glabrata, this pathway has not yet been investigated. Finally, the glucose repression pathway ensures repression of respiration and repression of the use of alternative carbon sources. This pathway is not well characterized in Candida species. It is important to note that, apart from glucose, other sugars and sugar-analogs, such as N-acetylglucosamine in the case of C. albicans, are also important carbon sources. In these fungal pathogens, sensing sugars is important for a number of virulence attributes, including adhesion, oxidative stress resistance, biofilm formation, morphogenesis, invasion, and antifungal drug tolerance. In this review, the sugar sensing and signaling mechanisms in these Candida species are compared to S. cerevisiae.