Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance.
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.
Ndieyira
Joseph Wafula
JW
London Centre for Nanotechnology, Departments of Medicine, University College London, 17-19 Gordon Street, London WC1H 0AH, UK.
Watari
Moyu
M
Barrera
Alejandra Donoso
AD
Zhou
Dejian
D
Vögtli
Manuel
M
Batchelor
Matthew
M
Cooper
Matthew A
MA
Strunz
Torsten
T
Horton
Mike A
MA
Abell
Chris
C
Rayment
Trevor
T
Aeppli
Gabriel
G
McKendry
Rachel A
RA
D001419:Bacteria / Q000166:cytology / Q000187:drug effects; D001665:Binding Sites / Q000502:physiology; D015374:Biosensing Techniques / Q000639:trends*; D002462:Cell Membrane / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects*; D046210:Microfluidic Analytical Techniques / Q000639:trends; D018625:Microscopy, Atomic Force / Q000639:trends; D009088:Mucoproteins / Q000737:chemistry* / Q000378:metabolism; D036103:Nanotechnology / Q000639:trends*; D012680:Sensitivity and Specificity; D013312:Stress, Physiological; D013718:Tensile Strength; D014640:Vancomycin / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
D008565:Membrane Proteins; D009088:Mucoproteins; D014640:Vancomycin