Related Experiment Video

Updated: Dec 31, 2025

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
11:15

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations

Published on: July 24, 2021

5.3K

Effect of tolerance on the evolution of antibiotic resistance under drug combinations

Jiafeng Liu1, Orit Gefen1, Irine Ronin1

  • 1Racah Institute of Physics, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem, Israel.

Science (New York, N.Y.)
|January 11, 2020
PubMed

Insights

Drug tolerance, not just resistance, accelerates the evolution of antibiotic resistance in Staphylococcus aureus. This finding is crucial for developing new combination therapies to combat bacterial infections effectively.

Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Pharmacology

Background:

  • Drug combinations are standard for preventing antimicrobial resistance.
  • The role of tolerance, a distinct survival mechanism, in combination therapy efficacy is poorly understood.

Purpose of the Study:

  • To investigate the impact of tolerance on the evolution of resistance in Staphylococcus aureus under combination antibiotic treatment.
  • To elucidate the mechanisms by which tolerance promotes resistance development.

Main Methods:

  • Monitoring Staphylococcus aureus strains from patients undergoing combination treatment.
  • Conducting in vitro evolution experiments with clinical isolates.
  • Testing the effect across different antibiotic classes.

Main Results:

  • Tolerance mutations emerged rapidly in patients, preceding resistance development despite combination therapy.
  • In vitro experiments demonstrated that tolerance facilitates the evolution of resistance under combination treatments.
  • The observed effect of tolerance was consistent across various antibiotic classes.

Conclusions:

  • Tolerance is a significant factor that can accelerate the evolution of resistance, even with combination therapies.
  • Future combination treatment strategies must account for tolerance to effectively prevent resistance.
  • Understanding tolerance mechanisms is vital for designing more robust antimicrobial therapies.

More Related Videos

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance09:00

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

12.2K
High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method07:51

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method

Published on: May 21, 2018

12.4K

Related Concept Videos

Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
6.6K
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
1.0K
Antibiotic Selection00:57

Antibiotic Selection

Overview
59.2K
Transduction01:16

Transduction

Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
1.0K
Antimicrobial Effectiveness01:28

Antimicrobial Effectiveness

The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
857
Combined Effects of Drugs: Antagonism01:30

Combined Effects of Drugs: Antagonism

The combined effects of drugs can result in various interactions, of which an important type is antagonism. Antagonism is a mechanism where one drug inhibits or counteracts the effects of another drug. Antagonism can occur through various means, including receptor binding, allosteric modulation, functional interaction, chemical reactions, and pharmacokinetic processes.
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
11.4K