Combatting Pathogenic Bacteria with Synthetic Immunotherapeutics from Chitosan: Antibody Recruiting at Engineered Bacterial Surface with Peptidoglycan Analogs

Abstract

The emergence of microbial drug resistance, coupled with the paucity of new antibiotics poses an impending threat to public health. In this work, we drew inspiration from synthetic peptidoglycan oligomers and successfully constructed antibody-recruiting peptidoglycan analogs, 2a-d, with excellent safety profiles and high efficiencies in recruiting antibodies across different conditions. Further, we demonstrated that these peptidoglycan analogs could be readily incorporated into bacteria cell walls, whereby both simple monoclonal and pooled human serum antibodies effectively congregated to the surface-engineered bacteria, leading to the complete extermination of the engineered bacterial cells both in vitro and in vivo. Our peptidoglycan analog agents for recruiting endogenous antibodies to combat pathogenic bacteria enable further development of promising broad-spectrum immunotherapeutics.