Characterisation of immunostimulatory compounds in streptococcus pneumoniae towards understanding the host pathogen interaction / Ezarina Abdul Rahim

Streptococcus pneumoniae is a common cause of morbidity and mortality worldwide. S. pneumoniae cause many types of infections such as meningitis, bacteremia, sepsis, acute sinusitis, and otitis media. S. pneumoniae has more than 92 different serotypes based on its capsular structure. The aim of the study is to investigate the effect of serotypic variation on genes encoding virulent determinants in relation to capsular properties, the role played by the neuraminidase in the colonisation and the patterns of toll-like receptor signaling responses in A549 human lung epithelial cell line towards understanding the host pathogen interaction. In this study, serotype 14 appears to have an additional chemical shift peak by using proton nuclear magnetic resonance (NMR), thus may be the reasons of reduced affinity to penicillin. The sequence variation in pneumococcal genes was observed by using polymerase chain reaction. The differential expression level of neuraminidase was done using reverse transcription polymerase chain reaction. Higher NanA gene expression in serotype 23F and 19F suggests that these serotypes are more invasive. In contrast, NanB gene showed lowlevel expression in serotype 23F and 19F. This postulates that NanA and NanB gene may have different function or mechanism in the pathogenesis of S. pneumoniae. Lastly, the toll-like receptor (TLR) signaling responses in A549 cells upon infection with pneumococcal cell wall were investigated by using RT² Profiler PCR Array. The involvements of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 and TLR10 in modulating the immune response were detected. TLR2 showed the highest expression indicates it is important in recognition of cell wall components. Serotype 1, 3, and 5 that able to induce higher TNFα and IL-1α have shown to be more immunogenic. The study would give a better insight into pneumococcal pathogenesis and host pathogen interaction in relation to different serotypes.