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Updated: Mar 1, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

Published on: October 25, 2013

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Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci

Sean E Pidgeon1, Marcos M Pires1

  • 1Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.

ACS Chemical Biology
|June 3, 2017
PubMed

Insights

A novel metabolic probe tracks how vancomycin-resistant enterococci (VRE) change their cell walls to resist antibiotics. This tool helps visualize drug resistance and study VRE's complex defense mechanisms.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Drug-resistant bacterial infections, particularly vancomycin-resistant enterococci (VRE), pose a significant global health threat.
  • VRE develops resistance by altering cell wall biosynthesis pathways, evading the action of antibiotics like vancomycin.
  • Understanding the mechanisms of VRE resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To develop and utilize a novel metabolic probe for real-time monitoring of VRE phenotypic plasticity and cell wall remodeling in response to vancomycin.
  • To investigate the kinetics of drug resistance induction in VRE using synthetic cell wall analogs.
  • To explore the potential of this probe in evaluating VRE response to various vancomycin analogs and other cell wall-targeting antibiotics.

Main Methods:

  • Design and synthesis of a cell wall analog to serve as a metabolic probe.
  • Application of the probe in live VRE cells to monitor cell wall structural alterations during vancomycin exposure.
  • Interrogation of VRE response to vancomycin analogs and other antibiotics using the developed probe.
  • Development of a proof-of-principle strategy for visual inspection of drug resistance induction.

Main Results:

  • The synthetic cell wall analog successfully monitored VRE cell wall remodeling and phenotypic changes in response to vancomycin.
  • The probe enabled tracking of the kinetics of drug resistance phenotype induction by hijacking the VRE resistant precursor biosynthetic pathway.
  • The study demonstrated the utility of the probe in assessing VRE responses to different antibiotic analogs and agents.
  • A visual method for inspecting drug resistance induction was successfully demonstrated.

Conclusions:

  • The developed metabolic probe is a valuable tool for studying VRE phenotypic plasticity and cell wall biosynthesis.
  • This probe facilitates the real-time elucidation of mechanisms underlying vancomycin resistance in VRE.
  • The findings pave the way for further research into the enzymes involved in VRE resistance and the development of new anti-infective strategies.

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