Synthetic Immunotherapeutics against Gram-negative Pathogens.
Cell Chem Biol
; 25(10): 1185-1194.e5, 2018 10 18.
Article
en En
| MEDLINE
| ID: mdl-29983273
ABSTRACT
While traditional drug discovery continues to be an important platform for the search of new antibiotics, alternative approaches should also be pursued to complement these efforts. We herein designed a class of molecules that decorate bacterial cell surfaces with the goal of re-engaging components of the immune system toward Escherichia coli and Pseudomonas aeruginosa. More specifically, conjugates were assembled using polymyxin B (an antibiotic that inherently attaches to the surface of Gram-negative pathogens) and antigenic epitopes that recruit antibodies found in human serum. We established that the spacer length played a significant role in hapten display within the bacterial cell surface, a result that was confirmed both experimentally and via molecular dynamics simulations. Most importantly, we demonstrated the specific killing of bacteria by our agent in the presence of human serum. By enlisting the immune system, these agents have the potential to pave the way for a potent antimicrobial modality.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Polimixina B
/
Pseudomonas aeruginosa
/
Infecciones por Pseudomonas
/
Escherichia coli
/
Infecciones por Escherichia coli
/
Antibacterianos
/
Epítopos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos