Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C60-Secondary Ion Mass Spectrometry

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 se...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2017-05, Vol.89 (9), p.5050-5057
Main Authors: Tian, Hua, Six, David A, Krucker, Thomas, Leeds, Jennifer A, Winograd, Nicholas
Format: Article
Language:English
Subjects:
Ampicillin
Analytical chemistry
Antibiotics
Bacteria
Cells
Chemistry
Drug development
E coli
Efflux
Escherichia coli
Gram-negative bacteria
Imaging
Mass spectrometry
Mass spectroscopy
Molecules
Secondary ion mass spectrometry
Spatial discrimination
Spatial resolution
Spectroscopy
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Summary: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.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.7b00466