phd-2021

Structural, biosynthetic and serological interaction studies of the capsular polysaccharides from Streptococcus pneumoniae

Streptococcus pneumoniae (the pneumococcus) is an encapsulated human pathogen, which has remained a major cause of morbidity and mortality globally among bacterial infectious disease, especially in infants and children. The crucial virulence of pneumococcus is the polysaccharide capsule that shields the bacterium from the host immune system. Moreover, there are near 100 different serotypes and each serotype has a unique capsular polysaccharide (CPS). As CPS can elicit the immune response to generate CPS specific antibodies, the purified CPS or CPS conjugates from prevalent or invasive serotypes are used as vaccines against pneumococcal infections. Therefore, a better understanding of pneumococcal CPS, their biosynthesis and immunologic activities will allow for better surveillance and regulation of the pathogen and its diseases.

The structural determination of unknown pneumococcal CPS can provide insights into the function of CPS biosynthetic genes, which is significant for diagnosis based on gene sequence methods. Moreover, as the immunogenic activities of CPS are based on the chemical structures, the elucidation of CPS structures can provide fundamental knowledge for understanding the antigenic properties of CPS. In this PhD project, the CPS structures from seven previously unknown pneumococcal CPS was determined by 1D and 2D NMR spectroscopy and other chemical analysis tools. Subsequently, the correlation of determined CPS structures with biosynthesis could allow us to predict the function of related biosynthetic genes and enzymes. A further serological cross-reaction and interaction study of CPS with diagnostic antisera provides a better understanding of the relationship between CPS structures and their immunologic activities.

To sum up, the combination of CPS structure, biosynthesis and serological interaction studies provided a better understanding of pneumococcal CPS, which can be useful for the development of better diagnostic methods and formulating future pneumococcal vaccines.

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Supervisors

Professor Jens Øllgaard Duus
Associate Professor Charlotte H. Gotfredse