Protein Glycosylation in pathogenic Gram-positive bacteria – Glyco-path

S. agalactiae [also known as Group B Streptococcus or GBS], a low % GC gram-positive cocci, is the foremost cause of severe infections in newborns. It is a common colonizer of the gastro-intestinal and urogenital tracts of up to 40% of healthy individuals. However in certain undefined circumstances, GBS can become a life-threatening pathogen. In about 80% of cases, neonatal GBS infection is acquired during delivery by direct mother-to-baby transmission through the oral or respiratory way. The development of GBS disease requires successful bacterial colonisation of the vaginal/digestive epithelium, translocation across placental or epithelial barriers, resistance to immune clearance in bloodstream and, in cases of meningitis, the ability to breach the endothelial blood–brain barrier.

Surface proteins are likely to play important roles during different stages of an infection, and particularly in the initial adhesion step. The recent discovery of protein glycosylation in Gram-negative mucosal pathogens in the last decade has revolutionized our way of envisaging host-pathogen interactions. Several virulence factors are covalently modified with carbohydrates and their role in pathogenesis has been demonstrated in animal models Like in eukaryotic organisms, N- and O-glycosylation systems have been identified in Gram-negative bacteria and were primarily associated with the modification of surface and secreted proteins. The first bacterial glycosylated proteins that were identified are abundant surface proteins like flagellins, pilins, and S-layer proteins. In Gram-negative bacteria,

Much less is known about protein glycosylation in Gram-positive pathogen. Except for S-layers proteins and a new family of serine-rich bacterial adhesins that are conserved in streptococcal and staphylococcal species, there is no current experimental evidence for protein glycosylation in Gram-positive pathogens. Our recent work on surface proteins of S. agalactiae, in particular our characterization of Srr1, a serine-rich surface glycoprotein required for virulence in mice constitutes the starting point of this project.

The main aim of this project is to identify the surface glycoproteome of S. agalactiae, through a combination of biochemical and genetic approaches, and to explore its role in pathogenesis using mammalian animal models