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Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry

[Image: see text] The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster...

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Autores principales: Tian, Hua, Six, David A., Krucker, Thomas, Leeds, Jennifer A., Winograd, Nicholas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415874/
https://www.ncbi.nlm.nih.gov/pubmed/28332827
http://dx.doi.org/10.1021/acs.analchem.7b00466
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author Tian, Hua
Six, David A.
Krucker, Thomas
Leeds, Jennifer A.
Winograd, Nicholas
author_facet Tian, Hua
Six, David A.
Krucker, Thomas
Leeds, Jennifer A.
Winograd, Nicholas
author_sort Tian, Hua
collection PubMed
description [Image: see text] The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) as a label-free approach to chemically map small molecules in aggregated and single Escherichia coli cells, with ∼300 nm spatial resolution and high chemical sensitivity. The feasibility of quantitative analysis was explored, and a nonlinear relationship between treatment dose and signal for tetracycline and ampicillin, two clinically used antibacterials, was observed. The methodology was further validated by the observation of reduction in tetracycline accumulation in an E. coli strain expressing the tetracycline-specific efflux pump (TetA) compared to the isogenic control. This study serves as a proof-of-concept for a new strategy for chemical imaging at the nanoscale and has the potential to aid discovery of new antibacterials.
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spelling pubmed-54158742017-05-05 Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry Tian, Hua Six, David A. Krucker, Thomas Leeds, Jennifer A. Winograd, Nicholas Anal Chem [Image: see text] The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) as a label-free approach to chemically map small molecules in aggregated and single Escherichia coli cells, with ∼300 nm spatial resolution and high chemical sensitivity. The feasibility of quantitative analysis was explored, and a nonlinear relationship between treatment dose and signal for tetracycline and ampicillin, two clinically used antibacterials, was observed. The methodology was further validated by the observation of reduction in tetracycline accumulation in an E. coli strain expressing the tetracycline-specific efflux pump (TetA) compared to the isogenic control. This study serves as a proof-of-concept for a new strategy for chemical imaging at the nanoscale and has the potential to aid discovery of new antibacterials. American Chemical Society 2017-03-23 2017-05-02 /pmc/articles/PMC5415874/ /pubmed/28332827 http://dx.doi.org/10.1021/acs.analchem.7b00466 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Tian, Hua
Six, David A.
Krucker, Thomas
Leeds, Jennifer A.
Winograd, Nicholas
Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title_full Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title_fullStr Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title_full_unstemmed Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title_short Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C(60)-Secondary Ion Mass Spectrometry
title_sort subcellular chemical imaging of antibiotics in single bacteria using c(60)-secondary ion mass spectrometry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415874/
https://www.ncbi.nlm.nih.gov/pubmed/28332827
http://dx.doi.org/10.1021/acs.analchem.7b00466
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