Sully, Erin K. Geller, Bruce L. Li, Lixin Moody, Christina M. Bailey, Stacey M. Moore, Amy L. Wong, Michael Nordmann, Patrice Daly, Seth M. Sturge, Carolyn R. Greenberg, David E. 2017-03-01 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. application/pdf https://folia.unifr.ch/global/documents/305511 https://folia.unifr.ch/documents/305511/files/nor_pcp.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1093/jac/dkw476 info:eu-repo/semantics/openAccess License undefined Journal of Antimicrobial Chemotherapy. - 2017, vol. 72, no. 3, p. 782–790 info:eu-repo/classification/udc/57 Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo http://purl.org/coar/resource_type/c_6501