Bacteriology Core

Abstract The collective goal of this collaborative P01 application is to target glycans on the surface of bacterial pathogens using antibodies as anti-infectious agents. We hypothesize that antibodies targeting bacterial glycans with high affinity will be effective in combating antibiotic-resistant bacterial pathogens. In the specific projects of this application, anti-glycan antibodies will be developed against selected surface glycan targets on the most serious bacterial pathogens, including methicillin-resistant Staphylococcus aureus (Sa), carbapenem-resistant Enterobacteriaceae (Klebsiella pneumoniae or Kp), and antibiotic resistant Neisseria gonorrhoeae (Ng), all of which are on the “High Priority” or “Critical Priority” list of the World Health Organization (WHO). The goal of this Core will be to serve the bacteriology needs of the P01 Team. Our initial focus will be to test the developed anti- glycan antibodies against live Sa pathogen using a series of assays, including antibody binding affinity, antibody specificity, and opsonophagocytic killing potency. Next, we will assess the impact of the antibodies on promoting complement mediated killing. In parallel we will test developed anti-glycan antibodies against live Kp and Ng pathogens and repeat each of the antibody binding and killing assays. Finally, we will test selected anti-Sa antibodies in a mouse model of skin infection and provide the P01 team with new glycan target leads for development. The outcomes of this collaborative project will include a better understanding of how the immune system can target antibiotic-resistant bacteria and how immune responses can be used to control bacterial growth without causing resistance to arise.