Thushara Galbadage
Molecular Nanomachines Disrupt Bacterial Cell Wall, Increasing Sensitivity of Extensively Drug-Resistant Klebsiella pneumoniae to Meropenem
Galbadage, Thushara; Liu, Dongdong; Alemany, Lawrence B.; Pal, Robert; Tour, James M.; Gunasekera, Richard S.; Cirillo, Jeffrey D.
Authors
Dongdong Liu
Lawrence B. Alemany
Professor Robert Pal robert.pal@durham.ac.uk
Professor
James M. Tour
Richard S. Gunasekera
Jeffrey D. Cirillo
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.
Citation
Galbadage, T., Liu, D., Alemany, L. B., Pal, R., Tour, J. M., Gunasekera, R. S., & Cirillo, J. D. (2019). Molecular Nanomachines Disrupt Bacterial Cell Wall, Increasing Sensitivity of Extensively Drug-Resistant Klebsiella pneumoniae to Meropenem. ACS Nano, 13(12), 14377-14387. https://doi.org/10.1021/acsnano.9b07836
Journal Article Type | Article |
---|---|
Acceptance Date | Dec 9, 2019 |
Online Publication Date | Dec 9, 2019 |
Publication Date | Dec 24, 2019 |
Deposit Date | Jan 10, 2020 |
Publicly Available Date | Dec 9, 2020 |
Journal | ACS Nano |
Print ISSN | 1936-0851 |
Electronic ISSN | 1936-086X |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 13 |
Issue | 12 |
Pages | 14377-14387 |
DOI | https://doi.org/10.1021/acsnano.9b07836 |
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Copyright 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
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