AVS 56th International Symposium & Exhibition
    Applied Surface Science Thursday Sessions
       Session AS2+BI-ThM

Paper AS2+BI-ThM4
Nanomechanics of Glycopeptide Resistant Superbugs and Superdrugs

Thursday, November 12, 2009, 9:00 am, Room K

Session: Scanning Probe Studies of Biological Materials
Presenter: J. Ndieyira, Uni. College London, UK and Jomo Kenyatta Univ. of Agriculture and Tech., Kenya
Authors: J. Ndieyira, Uni. College London, UK and Jomo Kenyatta Univ. of Agriculture and Tech., Kenya
A. Donoso Barrera, Uni. College London, UK
M. Vogtli, Uni. College London, UK
M. Sushko, Uni. College London, UK and PNNL
D. Zhou, Univ. of Leeds, UK
M. Cooper, The Univ. of Queensland, Australia
C. Abell, Univ. of Cambridge, UK
T. Strunz, Uni. College London, UK
G. Aeppli, Uni. College London, UK
R. McKendry, Uni. College London, UK
Correspondent: Click to Email

The discovery of penicillin in 1928 marked the beginning of a remarkable new era of antibiotic ‘wonder drugs’, saving millions of lives across the world. However the widespread and often indiscriminate use of antibiotics has fuelled the alarming growth of antibiotic resistant superbugs, including methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE). To remain one step ahead of the superbugs, there is now an urgent need to develop new antibiotics and yet the drug pipeline is severely limited. We recently reported the nanomechanical detection of vancomycin-cell wall peptide interactions on cantilever arrays and discriminated between vancomycin-sensitive and vancomycin-resistant phenotypes.1 In this talk I will present our new work which exploits this technology for the search of new superdrugs active against VRE. We have investigated a series of vancomycin derivatives and detect a dramatic enhancement in surface binding affinities compared to homogeneous solution measurements. We identify a glycopeptide which binds 11,000 more strongly to resistant peptide analogues. Our findings reveal fundamental new insights into the mechanism of antibiotic bindings to a model bacterial cell wall peptides using nanosensors, which not only has important implications on the design of new devices with significantly improved antibiotic detection sensitivity but will also impact on our understanding of the mode of action of antibiotics on intact bacteria. These findings highlight the potential of BioMEMs devices for application in pharmaceutical industry and will accelerate the discovery of new antibiotics.

[1] ‘Nanomechanical detection of antibiotic mucopeptide binding in a model for superbug drug resistance.’ Ndieyira, W.N, Watari, M., Donoso-Barrera, A., Batchelor, M., Zhou, D., Vogtli, M., Bactchelor, M., Cooper, M., Strunz, T., Abell, C.A., Rayment, T., Aeppli, G. & McKendry R.A. Nature Nanotechnology 3, 691 - 696 (2008). Also featured in Nature Nanotechnology News and Views, BBC, New Scientist, Physics Today, Chemistry World, UK T&I.