Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance.
Nat Commun
; 14(1): 5311, 2023 09 01.
Article
em En
| MEDLINE
| ID: mdl-37658047
ABSTRACT
The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacorresistência Bacteriana
/
Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article