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Abstract
To date, Streptococcus pneumoniae (Spn) remains a high-risk commensal that can cause invasive pneumococcal diseases like pneumonia, otitis media, bacteremia and meningitis. The pneumococcal glycoconjugate vaccines have been effective against most of the included serotypes in the vaccine to reduce incidence rates in children. However, with over 100 serotypes in existence, an increase in non-encapsulated strains, and the potential for serotype switching and antibiotic resistance, the need for a protein-based, serotype independent vaccine has grown. We hypothesized that the pneumococcal serine-rich repeat protein (PsrP), the only known glycoprotein in Spn, has roles of bacterial virulence and interactions with host lung cells due to its novel and uncharacterized glycans. In this dissertation, we aimed to better understand the role of surface glycans on PsrP and assess its potential as a next generation glycoprotein vaccine. We provide evidence that the glycosyltransferases that modify PsrP are necessary for protein function and virulence. Additionally, we show PsrP prevalence among serotypes at the global scale and demonstrate the potential PsrP has for serotype coverage. Finally, we begin to employ bioconjugation strategies towards PsrP to investigate what the mature glycans are on the protein and produce a bioconjugate vaccine. These studies have enhanced our understanding of PsrP towards the pneumococcus and may influence further research into PsrP as a conserved glycoprotein vaccine candidate for serotype independent vaccine design.