Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo.
J Antimicrob Chemother
; 72(3): 782-790, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-27999041
ABSTRACT
Objectives:
The objective of this study was to test the efficacy of an inhibitor of the New Delhi metallo-ß- lactamase (NDM-1). Inhibiting expression of this type of antibiotic-resistance gene has the potential to restore antibiotic susceptibility in all bacteria carrying the gene.Methods:
We have constructed a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) that selectively inhibits the expression of NDM-1 and examined its ability to restore susceptibility to meropenem in vitro and in vivo .Results:
In vitro , the PPMO reduced the MIC of meropenem for three different genera of pathogens that express NDM-1. In a murine model of lethal E. coli sepsis, the PPMO improved survival (92%) and reduced systemic bacterial burden when given concomitantly with meropenem.Conclusions:
These data show that a PPMO can restore antibiotic susceptibility in vitro and in vivo and that the combination of PPMO and meropenem may have therapeutic potential against certain class B carbapenem-resistant infections in multiple genera of Gram-negative pathogens.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Beta-Lactamasas
/
Tienamicinas
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Enterobacteriaceae
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Carga Bacteriana
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Morfolinos
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Antibacterianos
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2017
Tipo del documento:
Article