Cathy Rowland, United Kingdom
University of Warwick School of Life ScienceAuthor Of 1 Presentation
IMPACT OF BINDING RESPIRATORY SYNCYTIAL VIRUS ON PNEUMOCOCCAL CELL DIVISION AND ANTIBIOTIC SENSITIVITY (ID 214)
Abstract
Background
There is increasing evidence that severe pneumococcal disease is associated with coinfection with respiratory syncytial virus (RSV). Our previous work demonstrated a direct interaction between these pathogens, with RSV glycoprotein (RSV-G) binding penicillin binding protein (PBP) 1a of S. pneumoniae. This interaction led to enhanced virulence in a murine pneumonia model. This study aimed to determine the mechanism behind this, by examining the direct effects of RSV-G on PBP1a activity and bacterial division.
Methods
Clinical pneumococcal strains were screened for their ability to bind a purified recombinant RSV-G using immunoblot assays, fluorescence and electron microscopy. The effect on PBP1a activity was determined using enzymatic assays and by testing antibiotic susceptibility.
Results
Using fluorescent amino acid pulse labelling we observed RSV-G binding to the site of active pneumococcal cell wall synthesis. Following RSV-G exposure, pneumococci had morphological defects and increased lysis compared to controls, but growth rate was not reduced. PBP1a glycosyltransferase activity was not inhibited by RSV-G, while some pneumococci exhibited enhanced penicillin sensitivity.
Conclusions
RSV-G results in increased pneumococcal cell wall abnormalities and cell lysis. This may enhance pneumococcal virulence through the increased release of pneumolysin toxin. The implicated role of PBPs in RSV-G binding may be relevant to beta-lactam antibiotic usage.