Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota.
Commun Biol
; 4(1): 47, 2021 01 08.
Article
en En
| MEDLINE
| ID: mdl-33420317
ABSTRACT
The occurrence and spread of multidrug-resistant pathogens, especially bacteria from the ESKAPE panel, increases the risk to succumb to untreatable infections. We developed a novel antimicrobial peptide, Pam-3, with antibacterial and antibiofilm properties to counter this threat. The peptide is based on an eight-amino acid carboxyl-terminal fragment of human ß-defensin 1. Pam-3 exhibited prominent antimicrobial activity against multidrug-resistant ESKAPE pathogens and additionally eradicated already established biofilms in vitro, primarily by disrupting membrane integrity of its target cell. Importantly, prolonged exposure did not result in drug-resistance to Pam-3. In mouse models, Pam-3 selectively reduced acute intestinal Salmonella and established Citrobacter infections, without compromising the core microbiota, hence displaying an added benefit to traditional broad-spectrum antibiotics. In conclusion, our data support the development of defensin-derived antimicrobial agents as a novel approach to fight multidrug-resistant bacteria, where Pam-3 appears as a particularly promising microbiota-preserving candidate.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Salmonelosis Animal
/
Infecciones por Enterobacteriaceae
/
Microbioma Gastrointestinal
/
Enfermedades Gastrointestinales
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article