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

Authors :
Richard S. Gunasekera
Lawrence B. Alemany
Jeffrey D. Cirillo
Robert Pal
James M. Tour
Thushara Galbadage
Dongdong Liu
Source :
ACS nano, 2019, Vol.13(12), pp.14377-14387 [Peer Reviewed Journal]
Publication Year :
2019
Publisher :
American Chemical Society (ACS), 2019.

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.

Details

ISSN :
1936086X and 19360851
Volume :
13
Database :
OpenAIRE
Journal :
ACS Nano
Accession number :
edsair.doi.dedup.....e49ee3c8ca440eaef5e9811f3500d471
Full Text :
https://doi.org/10.1021/acsnano.9b07836