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Nutrient Gradients Mediate Complex Colony-Level Antibiotic Responses in Structured Microbial Populations
Mirjana Stevanovic1, Thomas Boukéké-Lesplulier2,3, Lukas Hupe2,4
1Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
Frontiers in Microbiology
|May 16, 2022
Summary
Bacterial antibiotic resistance is complex. This study reveals how nutrient gradients and gene expression in bacterial colonies create dynamic resistance, improving survival against tetracycline treatments.
Area of Science:
- Microbiology
- Systems Biology
- Biophysics
Background:
- Antibiotic treatments can fail due to individual bacterial cell heterogeneity.
- Structured bacterial populations like biofilms exhibit nutrient gradients affecting drug susceptibility.
- Coordination of antibiotic resistance gene expression across populations with environmental coupling is not well understood.
Purpose of the Study:
- To investigate the collective mechanisms of antibiotic resistance in spatially extended bacterial populations.
- To understand how spatiotemporal environmental coupling influences drug resistance regulation.
- To explore the dynamic interplay between cell growth, gene expression, and antibiotic response.
Main Methods:
- Utilized a custom microfluidic device to study tetracycline-resistant *E. coli* microcolonies.
- Applied precisely defined dynamic drug regimens to observe cellular and population-level responses.
- Developed a mathematical model integrating metabolism and gene expression regulation.
Main Results:
- Observed intricate interplay between drug-induced growth changes and growth-dependent resistance gene expression.
- Found redistribution of metabolites and reorganization of growth patterns within colonies.
- Demonstrated dynamic phenotypic structures that enhance colony growth and population-level resistance during drug exposure.
Conclusions:
- Collective bacterial responses to antibiotics involve dynamic phenotypic structures driven by environmental feedback.
- Understanding these principles is crucial for designing effective antibiotic treatment strategies.
- Mathematical modeling can capture the complex spatiotemporal dynamics of antibiotic resistance in bacterial colonies.
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