A structure-function analysis of the exo-beta-D-N-acetylglucosaminidase StrH, an important Streptococcus pneumoniae virulence factor.

Streptococcus pneumoniae is a common bacterium that can cause serious infections like acute respiratory disease (pneumonia), infections of the brain and central nervous system (meningitis), blood infections (septicaemia, sometimes leading to sepsis), and ear infections (otitis media). This organism is one of the leading causes of death from infectious disease across the globe. In addition to showing a lethal synergism with the influenza virus, many strains of S. pneumoniae are rapidly becoming resistant to antibiotics and some strains have even been dubbed ""superbugs. From the practical perspective of combating S. pneumonia, there is a clear need to better understand how it makes us sick. Numerous studies have revealed that the ability of this germ to cause disease strongly depends on it attacking the sugars present in its host's tissues. Dr. Pluvinage’s work focuses on one protein that performs this type of function, a large enzyme called StrH, which is necessary for S. pneumoniae to infect its most commonly targeted human organs, the lungs and the ears. StrH is responsible for removing an abundant sugar (N-acetylglucosamine) from the surface of host cells and the protective sugar layers found in mucus. Though the activity of StrH is known, precisely how it performs its job is not. Consequently, Dr. Pluvinage is working to characterize the protein's complex, three-dimensional structure in order to better understand the protein's function. The results of this research will provide a foundation for generating new small molecular inhibitors that might allow for the effective treatment of infections caused by S. pneumoniae “superbugs”.