Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo.

Autor:	Sully EK; Department of Microbiology, Oregon State University, Corvallis, OR, USA., Geller BL; Department of Microbiology, Oregon State University, Corvallis, OR, USA., Li L; Department of Microbiology, Oregon State University, Corvallis, OR, USA., Moody CM; Department of Microbiology, Oregon State University, Corvallis, OR, USA., Bailey SM; Sarepta Therapeutics, Cambridge, MA, USA., Moore AL; Sarepta Therapeutics, Cambridge, MA, USA., Wong M; Sarepta Therapeutics, Cambridge, MA, USA.; Division of Infectious Diseases, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA., Nordmann P; Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland., Daly SM; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA., Sturge CR; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA., Greenberg DE; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2017 Mar 01; Vol. 72 (3), pp. 782-790.
DOI:	10.1093/jac/dkw476
Abstrakt:	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. (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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