Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo
- Sully, Erin K. Department of Microbiology, Oregon State University, Corvallis, USA
- Geller, Bruce L. Department of Microbiology, Oregon State University, Corvallis, USA
- Li, Lixin Department of Microbiology, Oregon State University, Corvallis, USA
- Moody, Christina M. Department of Microbiology, Oregon State University, Corvallis, USA
- Bailey, Stacey M. Sarepta Therapeutics, Cambridge, MA, USA
- Moore, Amy L. Sarepta Therapeutics, Cambridge, MA, USA
- Wong, Michael Sarepta Therapeutics, Cambridge, MA, USA
- Nordmann, Patrice Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
- Daly, Seth M. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA
- Sturge, Carolyn R. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA
- Greenberg, David E. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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01.03.2017
Published in:
- Journal of Antimicrobial Chemotherapy. - 2017, vol. 72, no. 3, p. 782–790
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Médecine 3ème année
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 288697
- DOI 10.1093/jac/dkw476
- Persistent URL
- https://folia.unifr.ch/unifr/documents/305511
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