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Updated: Jul 31, 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

Do Multiple Drug Resistance Transporters Interfere with Cell Functioning under Normal Conditions?

D A Knorre1,2, K V Galkina3, T Shirokovskikh4

  • 1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia. knorre@belozersky.msu.ru.

Biochemistry. Biokhimiia
|March 11, 2021
PubMed

Insights

Eukaryotic cells use drug-efflux transporters to combat toxins, but these systems can have unintended costs. Understanding these limitations may help overcome drug resistance in fungi.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Microbiology

Background:

  • Eukaryotic cells possess defense mechanisms against toxic compounds, including plasma membrane transporters conferring multiple drug resistance (MDR).
  • These MDR transporters, such as ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporters, efflux xenobiotics using cellular energy.
  • This review examines the potential drawbacks of active drug-efflux systems, using yeast as a model.

Purpose of the Study:

  • To discuss the potential costs associated with active drug-efflux systems in eukaryotic cells.
  • To explore how the inherent properties of MDR transporters can negatively impact cellular functions.
  • To propose strategies for counteracting multidrug resistance by exploiting the limitations of these efflux systems.

Main Methods:

  • Review of existing literature on MDR transporters, focusing on yeast models.
  • Analysis of the biochemical and cellular consequences of MDR transporter activity.
  • Speculative analysis of therapeutic strategies targeting MDR.

Main Results:

  • Pleiotropic drug resistance (PDR) subfamily ABC-transporters consume ATP constitutively.
  • MDR transporters can possess flippase activity, potentially disrupting plasma membrane integrity.
  • Excessive transporter activity may lead to unintended efflux of essential metabolites and interfere with cell-to-cell communication.

Conclusions:

  • Active drug-efflux systems, while protective, incur significant cellular costs.
  • Overactivity of MDR transporters can compromise cell membrane properties and disrupt cellular processes.
  • Targeting the limitations of drug-efflux mechanisms presents a promising avenue for combating multidrug resistance, particularly in pathogenic fungi.

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