Intermediate Levels of Antibiotics May Increase Diversity of Colony Size Phenotype in Bacteria
Related Experiment Video
Updated: Feb 5, 2026

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Lewis Lee1, Van M Savage1,2,3, Pamela J Yeh2,3
1Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, USA.
Abstract:
Antibiotics select for resistant bacteria whose existence and emergence is more likely in populations with high phenotypic and genetic diversity. Identifying the mechanisms that generate this diversity can thus have clinical consequences for drug-resistant pathogens. We show here that intermediate levels of antibiotics are associated with higher levels of phenotypic diversity in size of colony forming units (cfus), within a single bacterial population. We examine experimentally thousands of populations of bacteria subjected to different disturbance levels that are created by varying antibiotic concentrations. Based on colony sizes, we find that intermediate levels of antibiotics always result in the highest phenotypic variation of this trait. This result is supported across bacterial densities and in the presence of three different antibiotics with two different mechanisms of action. Our results suggest intermediate levels of a stressor (as opposed to very low or very high levels) could affect the phenotypic diversity of a population, at least with regards to the single trait measured here. While this study is limited to a single phenotypic trait within a single species, the results suggest examining phenotypic and genetic variation created by disturbances and stressors could be a promising way to understand and limit variation in pathogens.
Insights
Intermediate antibiotic levels increase bacterial phenotypic diversity, specifically in colony size. Understanding how stressors create this variation is key to combating drug-resistant pathogens.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Antibiotic resistance in pathogens is a growing clinical concern.
- Bacterial populations with high diversity are more likely to develop resistance.
- Mechanisms generating bacterial diversity are crucial for understanding pathogen evolution.
Purpose of the Study:
- To investigate the relationship between antibiotic concentration and bacterial phenotypic diversity.
- To determine if intermediate antibiotic levels influence phenotypic variation.
Main Methods:
- Experimentally exposing thousands of bacterial populations to varying antibiotic concentrations.
- Measuring phenotypic diversity based on colony forming unit (cfu) size.
- Testing across different bacterial densities and with multiple antibiotics.
Main Results:
- Intermediate antibiotic concentrations consistently resulted in the highest phenotypic diversity in colony size.
- This effect was observed across various bacterial densities and antibiotic types.
- The findings held true for antibiotics with different mechanisms of action.
Conclusions:
- Intermediate levels of stressors, like antibiotics, can significantly enhance phenotypic diversity within bacterial populations.
- This study highlights the importance of considering stressor intensity in understanding and potentially limiting pathogen variation.
- Further research into stress-induced phenotypic and genetic variation could offer new strategies against drug-resistant pathogens.
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