Mutant Group B Streptococcus surface expressed Phosphoglycerate kinase (PGK) with reduced plasminogen binding.

摘要

Group B streptococcus (GBS) is a Gram-positive streptococcus bacterium that can cause severe invasive disease in the human neonate. This can manifest as pneumonia, septicemia and meningitis. While antibiotic prophylaxis has reduced the incidence GBS disease in the neonatal population, it is still the one of the leading cause of neonatal invasive disease in North America including Alberta. Phosphoglycerate kinase (PGK), a glycolytic enzyme, has been demonstrated to be on the surface of GBS. Surface expressed GBS-PGK interacts with the hostcell protein plasminogen, which is thought to help bacteria invade further into the host by destruction of host barriers. In this thesis, a triple mutant GBS-PGK molecule PGK-M9 was created based on information from a space-filled model of PGK-plasminogen interaction sites. PGK-M9 bound 95% less plasminogen than the wild type GBS-PGK. This mutant will permit further investigation into the role of surface GBS-PGK in vivo models of GBS infection.