Journal article

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
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305511
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