Abstract
Friend or foe? Bacteria are often recognized for causing illness and fatal diseases, but many bacteria are harmless and can even serve beneficial roles in their hosts. In this doctoral work, Nelson Wang investigated both pathogenic and non-pathogenic (i.e. commensal) species from the genus Neisseria. Two human pathogens, N. gonorrhoeae and N. meningitidis, can cause the sexually transmitted infection gonorrhea and meningitis respectively. However, humans are also hosts to at least seven other closely related commensal neisserial species which do not cause disease. The studies presented in Wang’s thesis compare how one biological process, protein glycosylation, functions in both pathogenic and commensal Neisseria species.
Protein glycosylation is a post-translational modification present in all three domains of life. This process entails the attachment of sugars (i.e. glycans) to proteins by the actions of dedicated enzymes. Such glycans in bacteria are extremely diverse and can vary in composition, structure, and size. In bacteria, glycosylated proteins can aid the bacteria in adherence, mobility, and even virulence. The protein glycosylation (pgl) system in Neisseria was first characterized in N. gonorrhoeae and N. meningitidis and involves the attachment of mono-, di- or trisaccharide glycans. Recently, a functional pgl system was identified in N. elongata subsp. glycolytica, a distantly related, commensal species. However, the glycan found there is a tetrasaccharide, never before seen in the pathogenic species. In this doctoral work, Wang and colleagues discovered and characterized five novel pgl genes in N. elongata subsp. glycolytica.Through genetic, biochemical and mass spectrometric analyses, the functions of the new pgl gene products were also defined.
Although some pgl genes are conserved in pathogenic and commensal Neisseria species, each class of species were found to carry a specific subset of genes that defined their distinct glycan repertoires. The findings by Wang and colleagues thus established a clear association between glycan content and distinct types of host interaction.
In summary, the work of Wang and colleagues advances our understanding of the pgl system in Neisseria specifically and in other bacterial systems generally. By identifying the genetic basis for glycan diversity detected in the genus, this work also raised new questions into how related species evolve as either pathogens or commensals.