Abstract
Objectives: The objective of this study was to test the efficacy of an inhibitor of the New Delhi metallo-β- 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.
Original language | English (US) |
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Pages (from-to) | 782-790 |
Number of pages | 9 |
Journal | Journal of Antimicrobial Chemotherapy |
Volume | 72 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2017 |
ASJC Scopus subject areas
- Microbiology (medical)
- Pharmacology (medical)
- Infectious Diseases
- Pharmacology