Investigating the effect and impact of binding RSV-G protein on pneumococcal growth and antibiotic sensitivity (360G-Wellcome-212516_Z_18_Z)

The pneumococcus (Streptococcus pneumoniae) is a global pathogen associated with high mortality rates in young children and the elderly. My research has shown that pneumococci rapidly increase their virulence by binding to the G protein encoded by human respiratory syncytial virus (RSV), the leading cause of viral pneumonia. This is thought to be mediated by the pneumococcal receptor for RSV, penicillin binding protein 1a (PBP1a), an important protein involved in bacteria cell wall synthesis and cell division. However, the mechanism behind the increase in virulence remains unknown. This proposal builds on my recent observations and brings together world-leaders in the fields of virology and bacterial cell wall biosynthesis to determine the immediate phenotypic and genotypic consequences of the pneumococcus binding to RSV-G protein. To do this I will: Determine whether binding RSV-G protein affects pneumococcal growth and increases pneumococcal cell lysis. Determine the effect of RSV-G on PBP1a gene expression and the enzymatic activity of pneumococcal PBP1a. Determine whether binding to RSV-G protein increases pneumococcal antibiotic sensitivity. These findings will help direct a larger study to determine the mechanisms of virulence enhancement during co-infection and the impact this has on inflammation, the host cell response and, importantly, antimicrobial therapy.