Enhanced Synergism and Mechanism of Action Studies of Synthetic Antimicrobial Metallopeptides.
ChemMedChem
; 16(13): 2112-2120, 2021 07 06.
Article
en En
| MEDLINE
| ID: mdl-33825350
Antimicrobial peptides (AMPs) are found throughout most kingdoms of life, are an important part of host immunity, and have been shown to act synergistically in various organisms to ameliorate bacterial infections. Herein, we report the synergistic behavior observed between two AMPs, Sub5 and CP10A, against E. coli. In addition, enhanced synergistic activity against E. coli and MRSA 43300 for two derivatives of Sub5, extended with the amino-terminal copper and nickel (ATCUN) binding motif, is observed when dosed together with CP10A, while displaying little cytotoxicity towards human dermal fibroblasts. All three combinations of peptides co-localized within bacterial cells as evidenced by fluorescence confocal microscopy. Investigations into the mechanism of synergy shows that all peptides indirectly damage DNA within cells, while only the ATCUN derivatives can oxidize phospholipids. Combinations of peptides were also shown to upregulate the concentration of reactive oxygen species within both E. coli and MRSA 43300. These results suggest that the production of reactive oxygen species is an important aspect mechanistically and further highlights the potential of these metallopeptides to aid in the treatment of antibiotic-resistant infections.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Escherichia coli
/
Staphylococcus aureus Resistente a Meticilina
/
Péptidos Antimicrobianos
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania