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.

doi:10.1021/acsnano.9b07836

Molecular Nanomachines Disrupt Bacterial Cell Wall, Increasing Sensitivity of Extensively Drug-Resistant Klebsiella pneumoniae to Meropenem Thumbnail

Authors

Thushara Galbadage

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