Titolo della tesi: The host pathogen interactions in the Caenorhabditis elegans animal model: the role of glycosylation and a tool to screen for probiotic bacteria
In this project, the role of the
pmr 1 gene in the glycosylation process and i n the host microrganism
interaction was analyzed in C. elegans model system. Glycosylation produces a large number of
glycans, polysaccharides whose different morphology reflects the multiplicity of biological processes
in which they are involved. The emer ging role of glycans in the innate and acquired immunity of
vertebrates makes them a target for the study of the molecular mechanisms underlying the host
pathogen interaction, in order to develop new therapeutic approaches. The Ca 2+ ATPase, encoded by
the pmr 1 gene, appears to be involved in alterations of glycosylation mechanisms, as demonstrated by
studies on the homologous PMR 1 protein of Saccharomyces cerevisiae and Kluveromyces lactis . In
this work, pmr 1 mutant nematodes, obtained through RNA interf erence, were exposed to different
pathogenic microorganisms, showing an increased survival capacity compared to wild type
individuals, following infection by the Gram positive Staphylococcus aureus and Enterococcus
faecalis pathogens. This increased resist ance seems to be related to defects in the oligosaccharide
structure of glycoproteins of the cell surface caused by their altered glycosylation. The lack of regular
recognition of C. elegans surface glycoproteins by the two pathogens could, in fact, determ ine the
difficult adhesion of bacteria to the nematode and the reduction of their pathogenicity. Furthermore,
pmr 1 worms showed a different innate immune and oxidative stress responses, as well as an alteration
of the glycocalyx in their gut. Since glycos ylation is also involved in beneficial role of host microbiota
against pathogens, nematodes were used to preselect probiotic bacteria, whose efficacy will be
evaluate after administration on pmr 1 mutants, to measure the response of worms to pathogen
infec tion. Therefore, this study represents a first step in understanding the role of PMR 1 protein in the
host microrganism interaction in C. elegans