Induction of Endogenous Antibody Recruitment to the Surface of the Pathogen Enterococcus faecium.
Brianna E DalesandroMarcos M PiresPublished in: ACS infectious diseases (2020)
For the foreseeable future, conventional small molecule antibiotics will continue to be the predominant treatment option due to wide patient coverage and low costs. Today, however, there is already a significant portion of patients that fail to respond to small molecule antibiotics and, according to the Centers for Disease Control and Prevention, this number is poised to increase in the coming years. Therefore, this rise in drug resistant bacteria must be countered with the development of nontraditional therapies. We propose a measure based on the re-engagement of the immune system toward pathogenic bacteria by grafting bacterial cell surfaces with immunogenic agents. Herein, we describe a class of cell wall analogues that selectively graft bacterial cell surfaces with epitopes that promote their opsonization. More specifically, synthetic analogues of peptidoglycan conjugated to haptens were designed to be incorporated by the cell wall biosynthetic machinery into live Enterococcus faecium. E. faecium is a formidable human pathogen that poses a considerable burden to healthcare and often results in fatalities. We showed that treatment of E. faecium and vancomycin-resistant strains with the cell wall analogues led to the display of haptens on the cell surface, which induced the recruitment of antibodies existing in the serum of humans. These results demonstrate the feasibility in using cell wall analogues as the basis of a class of bacterial immunotherapies against dangerous pathogens.
Keyphrases
- cell wall
- small molecule
- drug resistant
- molecular docking
- healthcare
- biofilm formation
- cell surface
- single cell
- multidrug resistant
- end stage renal disease
- escherichia coli
- cell therapy
- chronic kidney disease
- newly diagnosed
- ejection fraction
- acinetobacter baumannii
- candida albicans
- protein protein
- stem cells
- gram negative
- structure activity relationship
- social media
- peritoneal dialysis
- pseudomonas aeruginosa
- oxidative stress
- photodynamic therapy
- high glucose
- risk factors
- mesenchymal stem cells
- case report
- pluripotent stem cells
- cystic fibrosis
- patient reported outcomes