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Updated: May 7, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development

Lejla Imamovic1, Morten O A Sommer

  • 1Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark.

Science Translational Medicine
|September 27, 2013
PubMed

Insights

Drug resistance is a major challenge. This study introduces collateral sensitivity cycling, a new sequential drug treatment strategy that combats resistance in bacterial infections and potentially cancer.

Area of Science:

  • Microbiology and Infectious Diseases
  • Pharmacology and Drug Resistance
  • Computational Biology and Network Analysis

Background:

  • Drug resistance poses a significant threat to managing infectious diseases and cancers.
  • Existing treatment strategies are insufficient to overcome the growing problem of antimicrobial and anticancer drug resistance.
  • Novel therapeutic approaches are urgently needed to combat resistance and improve patient outcomes.

Purpose of the Study:

  • To investigate collateral sensitivity and resistance profiles following drug exposure in Escherichia coli.
  • To develop a new treatment framework, collateral sensitivity cycling, to combat drug resistance.
  • To validate the efficacy of collateral sensitivity cycling in bacterial pathogens.

Main Methods:

  • Evolved drug resistance in Escherichia coli against 23 clinical drugs.
  • Mapped collateral sensitivity and resistance profiles to construct a complex network.
  • Identified and tested sequential drug combinations for collateral sensitivity cycling.

Main Results:

  • Discovered a complex collateral sensitivity network among drugs.
  • Identified hundreds of drug sets suitable for collateral sensitivity cycling.
  • Demonstrated that cyclic deployment of gentamicin and cefuroxime selects against resistance in pathogens.

Conclusions:

  • Collateral sensitivity cycling is a viable treatment paradigm for combating drug resistance.
  • This strategy shows potential for sustainable application in treating infectious diseases and cancers.
  • Findings provide proof of principle for a novel approach to overcome drug resistance.

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