Neisseria exhibits a general O-linked glycosylation system in which several surface exposed and periplasmic proteins are glycosylated. The major glycoprotein, PilE, is the building subunit of pili, which is an important virulence factor. The glycans can vary extensively due to phase variation of protein glycosylation (pgl) genes and polymorphic pgl gene content. The exact role of glycosylation in Neisseria remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to escape the human immune system and we will therefore study glycan diversity and immunogenicity.
PROGLYC aims to unravel protein glycosylation diversity and dynamics, as well as establish the role(s) of the O-linked protein glycosylation system in meningococcal carriage and disease, as well as investigate the potential for protein glycans as vaccine antigens for pathogenic Neisseria.
Bacterial meningitis is a serious global health problem and one of the major causative organisms is Neisseria meningitidis, which is also a common commensal in the upper respiratory tract of healthy humans and the only agent able to cause epidemics of meningitis. In bacteria, numerous loci involved in biosynthesis of surface exposed antigenic structures, such as outer lipopolysaccharides, lipoproteins, pili, flagella and other secreted proteins that are involved in the interaction between bacteria and host, are frequently subjected to homologous recombination and phase variation. These mechanisms are well described in Neisseria, and phase variation provides the ability to change these structures reversibly in response to the environment.
Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. It represents an emerging global health problem with increasing antibiotic resistance. There are no vaccine available and even natural infections fail to engender protective immunity. A successful vaccine against gonorrhea should therefore include numerous antigens to be able to stimulate a protective immune response. We are investigating the potential of protein glycans as vaccine antigens.
