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 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 affected 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 impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5 figures) plus Supplemental Material (6 pages, 3 figures). More details are available at http://www.london-nano.co

Introduction

In this introductory chapter, we discuss some of the challenges raised by the project of pluralization in the discipline of philosophy. We look at a few theoretical approaches to pluralization that this volume takes up—namely, the figure-based approach, the global approach, and the genre-based approach—and we consider what the pluralization project might also mean for philosophical pedagogy. Finally, we give a brief summary of the contributions in this volume and provide possible cross-references for each chapter

Introduction

In this introductory chapter, we discuss some of the challenges raised by the project of pluralization in the discipline of philosophy. We look at a few theoretical approaches to pluralization that this volume takes up-namely, the figure-based approach, the global approach, and the genre-based approach-and we consider what the pluralization project might also mean for philosophical pedagogy. Finally, we give a brief summary of the contributions in this volume and provide possible cross-references for each chapter