This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1) The protozoan parasite Toxoplasma gondii is a serious global pathogen that infects nearly one third of the adult human population. Despite its importance, very little is known about how this parasite initially engages a host cell in order to establish infection.
The aim of this proposal is to characterize the molecular interactions that enable T. gondii to attach to, and ultimately invade virtually every nucleated cell. More specifically, we will characterize the structural basis of how key members of a superfamily of developmentally expressed surface proteins on T. gondii (known as the SRS adhesins/antigens) mediate parasite attachment to host cells. Based on this work, we will be strategically poised to develop therapeutic interventions, either prophylactic or vaccine-based, to limit infectivity of this widespread zoonotic pathogen. 2)Pneumonia is an acute respiratory disease that is caused by viral or bacterial pathogens. The major causative agent, however, is the Gram positive bacterium Streptococcus pneumoniae. Invasive S. pneumoniae infections are a leading cause of death world-wide, with the hardest hit being the elderly and children less than 5 years old. In addition to pneumonia, this bacterium can cause meningitis, septicaemia, and otitis media. S. pneumoniae is clearly a serious pathogen that places a considerable burden on healthcare systems. Disturbingly, the frequency of antibiotic resistance in community acquired strains of S. pneumoniae is increasing requiring increased vigilance and redoubled research efforts aimed at fighting this bacterium. Our goal is to define the molecular mechanism of a family of S. pneumoniae encoded glycoside hydrolases with the ultimate goal of designing small molecule inhibitors.
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