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Molecular nanomachines disrupt bacterial cell wall, increasing sensitivity of extensively drug-resistant Klebsiella pneumoniae to Meropenem.

Galbadage, Thushara and Liu, Dongdong and Alemany, Lawrence B. and Pal, Robert and Tour, James M. and Gunasekera, Richard S. and Cirillo, Jeffrey D. (2019) 'Molecular nanomachines disrupt bacterial cell wall, increasing sensitivity of extensively drug-resistant Klebsiella pneumoniae to Meropenem.', ACS nano., 13 (12). pp. 14377-14387.

Abstract

Multidrug resistance in pathogenic bacteria is an increasing problem in patient care and public health. Molecular nanomachines (MNMs) have the ability to open cell membranes using nanomechanical action. We hypothesized that MNMs could be used as antibacterial agents by drilling into bacterial cell walls and increasing susceptibility of drug-resistant bacteria to recently ineffective antibiotics. We exposed extensively drug-resistant Klebsiella pneumoniae to light-activated MNMs and found that MNMs increase the susceptibility to Meropenem. MNMs with Meropenem can effectively kill K. pneumoniae that are considered Meropenem-resistant. We examined the mechanisms of MNM action using permeability assays and transmission electron microscopy, finding that MNMs disrupt the cell wall of extensively drug-resistant K. pneumoniae, exposing the bacteria to Meropenem. These observations suggest that MNMs could be used to make conventional antibiotics more efficacious against multi-drug-resistant pathogens.

Item Type:Article
Full text:(AM) Accepted Manuscript
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1021/acsnano.9b07836
Publisher statement:This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS nano copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsnano.9b07836
Date accepted:09 December 2019
Date deposited:10 January 2020
Date of first online publication:09 December 2019
Date first made open access:09 December 2020

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