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Updated: Oct 1, 2025

Stress-induced Antibiotic Susceptibility Testing on a Chip
Published on: January 8, 2014
The physiology and genetics of bacterial responses to antibiotic combinations
Roderich Roemhild1, Tobias Bollenbach2,3, Dan I Andersson4
1Institute of Science and Technology, Klosterneuburg, Austria.
Abstract:
Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy.
Insights
Understanding how bacteria respond to antibiotic combinations is key to fighting resistance. This review explores complex drug interactions and genetic mechanisms to improve antibiotic therapy.
Area of Science:
- Microbiology
- Pharmacology
- Genetics
Background:
- Antibiotic resistance is a growing threat, necessitating novel therapeutic strategies.
- Combining or cycling antibiotics shows promise but lacks a deep understanding of underlying mechanisms.
- Bacterial responses to antibiotics involve complex physiological stress and genetic mutations.
Purpose of the Study:
- To review current knowledge on bacterial physiology and genetics in response to antibiotics.
- To highlight mechanisms of synergistic and antagonistic antibiotic interactions.
- To discuss the clinical implications of antibiotic-drug and drug-resistance interactions.
Main Methods:
- Literature review of recent research on antibiotic interactions and resistance.
- Analysis of bacterial physiological stress responses to antibiotic exposure.
- Examination of genetic mechanisms, including resistance mutations and collateral sensitivity.
Main Results:
- Complex and unpredictable dynamics arise from combined antibiotic effects and resistance.
- Discovered mechanisms of synergistic and antagonistic drug interactions.
- Identified hysteresis in temporal antibiotic interactions and collateral effects of resistance mutations.
Conclusions:
- A unified understanding of drug and genetic interactions is crucial for advancing antibiotic therapy.
- Further research is needed to connect different phenomena and guide clinical applications.
- Improved knowledge can lead to more effective antibiotic treatment strategies.
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