Glycosylation is a key modification of proteins and lipids and it is involved in most intermolecular and intercellular interactions. Glycans play a variety of structural and functional roles in membrane and secreted proteins. During the course of an infection, bacterial cell surface play a critical role in the adherence to host tissues mediating interactions with the host environment and promoting colonization. Glycoconiugates are complex dynamic structures that can constantly change in response to different situations.
The nematode Caenorhabditis elegans is a simple model to study host-microrganism interaction, thanks to several advantages, among them the RNA interference tool leading to a rapid targeted investigation of gene function.
In this project C.elegans will be used to understand the role of glycosylation-related proteins in host-pathogen interactions and as useful model for mechanistic studies to exploit probiotic bacteria isolated from different substrates and to evaluate probiotic effects on nematodes physiology in glycosylation mutants. To this aim the role of the Ca2+-ATPase, encoded by pmr-1 gene in C.elegans glycosylation processes and in response to pathogens will be investigated. Then, nematode will be use to preselect probiotic bacteria, after that the efficacy of probiotics will be evaluate after administration on glycosylation mutants, to measure the response of worms to pathogen infection.
Glycosylation plays a major role in different biological processes, among which human diseases. Caenorhabditis elegans provides a powerful tool to study glycosylation, since this simple model has many genes homologous to mammalian genes involved in this process, suggesting that nematode can synthesize N-glycans, various O-glycans, glycolipids and chitin. Some of these genes can be cloned and expressed and the effects of mutations can be studied on worm development. Function of N-glycosylation could be explored studying the resistance of C. elegans to bacterial toxins and infections.
Glycoproteins contributed to pathogenesis mediating bacterial attachment to host. During this process, glycan expression is modulated by interaction between host and pathogen, influencing host immunity and gut glycosylation. In particular, gel-forming mucins, which are O-linked glycoproteins, normally protect from pathogens and physical and chemical attack, resulting an important aspect of innate defense. During the course of infection, mucin production, properties and barrier function change, highlighting that mucins are essential anti-parasitic effector molecules. Changes in glycosylation have been reported to be involved in cancer, inflammation and infection and may affect the functional properties of the mucus barrier. Hence, the study of glycoproteins and their role could lead to open up new therapeutic approaches that aim to protect the gut barrier and maintain its function, reducing gastrointestinal infections and regulating inflammatory conditions.
The C. elegans potentiality is due to the availability of mutants with deletions in genes with proven or putative function in glycosylation process; the ease to analyze glycan profiles can be define the biochemical functions of these genes and their involvement in the glycosylation pathways. Nematode is a useful model for studying the genetic basis for glycomic variation, which can also lead to therapeutic developments. Indeed, new infection eradication strategies may allow inhibition of bacterial adhesion to gut epithelial cells.
Therefore, many approaches could be adopted to modulate biological systems involving carbohydrates and lectin interactions, such as the use of glycomimetics to regulate the activity of lectins, modulation of genes and enzymes involved in glycosylation pathways.