Related Experiment Video
Updated: Jan 21, 2026
Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
Salicylate Increases Fitness Cost Associated with MarA-Mediated Antibiotic Resistance
Tiebin Wang1, Colin Kunze2, Mary J Dunlop3
1Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, Massachusetts; Biological Design Center, Boston University, Boston, Massachusetts.
Abstract:
Antibiotic resistance is generally associated with a fitness deficit resulting from the burden of producing and maintaining resistance machinery. This additional cost suggests that resistant bacteria will be outcompeted by susceptible bacteria in conditions without antibiotics. However, in practice, this process is slow in part because of regulation that minimizes expression of these genes in the absence of antibiotics. This suggests that if it were possible to turn on their expression, the cost would increase, thereby accelerating removal of resistant strains. Experimental and theoretical studies have shown that environmental chemicals can change the fitness cost associated with resistance and therefore have a significant impact on population dynamics. The multiple antibiotic resistance activator (MarA) is a clinically important regulator in Escherichia coli that activates downstream genes to increase resistance against multiple classes of antibiotics. Salicylate is an inducer of MarA that can be found in the environment and derepresses marA's expression. In this study, we sought to unravel the interplay between salicylate and the fitness cost of MarA-mediated antibiotic resistance. Using salicylate as an inducer of MarA, we found that a wide spectrum of concentrations can increase burden in resistant strains compared to susceptible strains. Induction resulted in rapid exclusion of resistant bacteria from mixed populations of antibiotic-resistant and susceptible cells. A mathematical model captures the process and predicts its effect in various environmental conditions. Our work provides a quantitative understanding of salicylate exposure on the fitness of different MarA variants and suggests that salicylate can lead to selection against MarA-mediated resistant strains. More generally, our findings show that natural inducers may serve to bias population membership and could impact antibiotic resistance and other important phenotypes.
Insights
Environmental inducers like salicylate can increase the fitness cost of antibiotic resistance in bacteria. This finding accelerates the removal of resistant strains, offering new strategies to combat antibiotic resistance.
Area of Science:
- Microbiology
- Evolutionary Biology
- Biochemistry
Background:
- Antibiotic resistance imposes a fitness cost on bacteria, theoretically leading to susceptible strains outcompeting resistant ones in antibiotic-free environments.
- Gene regulation often minimizes the expression of resistance mechanisms in the absence of antibiotics, slowing the removal of resistant bacteria.
- Environmental chemicals can modulate the fitness cost of antibiotic resistance, impacting bacterial population dynamics.
Purpose of the Study:
- To investigate the interaction between salicylate, an environmental inducer of the MarA regulator, and the fitness cost of MarA-mediated antibiotic resistance in Escherichia coli.
- To determine how salicylate affects the competitive fitness of antibiotic-resistant versus susceptible bacterial strains.
- To quantify the impact of salicylate on MarA-mediated resistance and its population-level consequences.
Main Methods:
- Utilized salicylate at various concentrations to induce the MarA regulator in antibiotic-resistant and susceptible bacterial strains.
- Assessed the fitness cost associated with MarA-mediated resistance by comparing the growth and competitive exclusion of resistant and susceptible bacteria in mixed populations.
- Developed and employed a mathematical model to simulate and predict the population dynamics under different salicylate exposure conditions and MarA variants.
Main Results:
- Salicylate induction significantly increased the fitness burden in antibiotic-resistant strains across a broad range of concentrations.
- Induction with salicylate led to the rapid exclusion of MarA-mediated resistant bacteria from mixed populations with susceptible counterparts.
- The mathematical model accurately captured the observed population dynamics and predicted outcomes under varying environmental scenarios.
Conclusions:
- Salicylate acts as a potent modulator of the fitness cost associated with MarA-mediated antibiotic resistance, promoting the selection against resistant strains.
- Natural environmental inducers can significantly influence bacterial population composition and the prevalence of specific phenotypes, including antibiotic resistance.
- Understanding these interactions provides quantitative insights into the environmental factors governing antibiotic resistance dynamics and suggests potential strategies for microbial population control.
More Related Videos
12:32Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
08:58Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Related Concept Videos
01:30Development of Antibiotic Resistance
00:57Antibiotic Selection
01:13Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
01:16Goodness-of-Fit Test
00:57Inclusive Fitness
01:25Increased Body Temperature