Streptococcus pneumoniae exists as over 100 antigenically distinct serotypes, as such, not all serotypes can be included in the vaccine, and vaccine serotypes were selected based on their disease burden. The introduction of pneumococcal conjugate vaccines was associated with a decrease in Invasive Pneumococcal Disease (IPD) caused by the vaccine serotypes, however IPD caused by non-vaccine serotypes subsequently increased. This increase is driven by changes in serotype distribution throughout the population, termed serotype replacement. Streptococcus pneumoniae is naturally transformable and during co-colonization with multiple pneumococcal serotypes, DNA from the capsular polysaccharide (CPS) locus can be exchanged causing serotype or capsule switching. Serotype switching is thought to play an important role in serotype replacement and vaccine escape, by introducing non-vaccine capsular polysaccharide DNA into vaccine type genetic lineages. Therefore, my research aims to identify and characterize serotype pairs with the potential for capsule switching, in order to assist the prediction of future serotypes of interest and further inform the development of next generation pneumococcal vaccines, ahead of an observed increase in disease burden at the population level.
My previous work at the University of Warwick, UK, focused on the structure-function relationship of proteins involved in peptidoglycan biosynthesis in Streptococcus pneumoniae and their impact on the development of penicillin resistance with the aim of identifying novel antimicrobial targets. During my undergraduate degree, my research focused on the enzymology of the cytoplasmic Mur ligases and my PhD focused on MurM. MurM is an aminoacyl-ligase which is responsible for creating branched precursors for indirect cross-linked peptidoglycan, and is required for high-level penicillin resistance. In the absence of an X-ray structure for MurM, we used homology modeling to obtain an improved understanding of this proteins' structure and it's interactions at the cytoplasmic membrane. We further characterized MurM enzymology with various cognate and non-cognate tRNA substrates, and the impact of hydrogen-peroxide (produced in copious amounts during aerobic growth of pneumococcus) on the charging of these tRNA substrates by tRNA synthetases.
My research at Yale focuses on the Capsular Polysaccharide (CPS) and serotype switching in Streptococcus pneumoniae. We recently developed a method for separating a pneumococcal serotype of interest from a mixed serotype sample in the laboratory setting. This is of particular importance with regards to conducting higher throughput serotype switch experiments using clinical or lab isolates, and this technique holds promise for the separation or enrichment of pneumococcus from clinical samples such as saliva.
Bacteria; Bacterial Vaccines; Cell Wall; Communicable Diseases; Microbiological Techniques; Microbiology; Molecular Biology; Penicillin Resistance; Peptidoglycan; Pneumococcal Infections; Pneumonia; Pneumonia, Pneumococcal; Polysaccharides, Bacterial; Streptococcus; Streptococcus pneumoniae; Bacterial Capsules; Gram-Positive Bacterial Infections; Community-Acquired Infections; Vaccines, Conjugate; Pneumococcal Vaccines; Structural Homology, Protein; Penicillin-Binding Proteins; Genome-Wide Association Study; Coinfection; Vaccine-Preventable Diseases
Antimicrobial Resistance; Emerging Infectious Diseases; Global Health; Respiratory Disease/Infections; Vaccines