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

TL;DR

This study demonstrates a nanomechanical, label-free method to detect antibiotic binding to bacterial cell wall analogues, providing insights into drug resistance mechanisms and potential for improved detection devices.

Contribution

It introduces a novel nanomechanical sensing approach for studying antibiotic-mucopeptide interactions, revealing the role of surface stress and percolation in drug resistance.

Findings

Detected vancomycin binding with 10 nM sensitivity in blood serum.

Quantified binding differences between sensitive and resistant mucopeptides.

Proposed a percolation-based model for surface stress related to drug binding.

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 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.