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Nanomechanical detection of antibiotic mucopeptide binding in a model for superbug drug resistance

DOI: 10.1038/nnano.2008.275 DOI Help
PMID: 18989336 PMID Help

Authors: Joseph Wafula Ndieyira (UCL) , Moyu Watari (UCL) , Dejian Zhou (Univ of Cambridge & Univ. of Leeds) , Manuel Vögtli (UCL) , Matthew Batchelor (University of Cambridge) , Matthew A. Cooper (University of Queensland) , Rachel A. Mckendry (UCL) , Torsten Strunz (UCL) , Mike A. Horton (UCL) , Chris Abell (University of Cambridge) , Trevor Rayment (Diamond Light Source) , Gabriel Aeppli ((UCL))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Nanotechnology , VOL 3 (11) , PAGES 691 - 696

State: Published (Approved)
Published: October 2008

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.

Subject Areas: Chemistry

Instruments: NONE-No attached Diamond beamline

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