Article abstract
Nature Nanotechnology 3, 691 - 696 (2008)
Published online: 12 October 2008 | doi:10.1038/nnano.2008.275
Subject Categories: Nanobiotechnology | Nanomedicine | Nanosensors and other devices | NEMS
Nanomechanical detection of antibiotic–mucopeptide binding in a model for superbug drug resistance
Joseph Wafula Ndieyira1,2,7, Moyu Watari1,7, Alejandra Donoso Barrera1, Dejian Zhou3,4, Manuel Vögtli1, Matthew Batchelor3, Matthew A. Cooper5, Torsten Strunz1, Mike A. Horton1, Chris Abell3, Trevor Rayment6, Gabriel Aeppli1 & Rachel A. McKendry1
Abstract
The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements have quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions activated by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also have an impact on our understanding of antibiotic drug action in bacteria.
- London Centre for Nanotechnology and Departments of Medicine and Physics, University College London, 17–19 Gordon Street, London WC1H 0AH, UK
- Jomo Kenyatta University of Agriculture and Technology, Department of Chemistry, PO Box 62000, Nairobi, Kenya
- Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
- School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
- These authors contributed equally to this work.
Correspondence to: Rachel A. McKendry1 e-mail: R.A.McKendry@ucl.ac.uk
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