Antibiotic Resistance Evolution in Bacterial Systems

The emergence and rapid spread of antibiotic resistance among bacterial pathogens constitutes a critical challenge to modern medicine. Resistance arises through genetic mutations and horizontal acquisition of resistance determinants, often facilitated by mobile genetic elements. Selective pressure from antibiotic use drives the fixation of resistant variants, which can exhibit cross-resistance to structurally unrelated drugs or collateral sensitivity that renders them vulnerable to alternative agents. Evolutionary trajectories are shaped by ecological context, bacterial lifestyle (for example planktonic versus biofilm growth) and pharmacodynamic parameters such as drug concentration and exposure time. Strategic deployment of antibiotics—through cycling, combination therapies or sequential regimens—can exploit evolutionary trade-offs to limit resistance emergence. Recent advances in high-throughput chemical genetics, experimental evolution and quantitative modelling have illuminated the complex networks of drug interactions and resistance pathways, informing rational designs for treatment protocols that suppress resistance while preserving therapeutic efficacy on a global scale.

Research from Nature Portfolio

Systematic mapping of antibiotic cross-resistance and collateral sensitivity using a genome-wide deletion library in Escherichia coli has expanded the known network of drug–drug interactions more than threefold. By validating inferred cross-resistance and collateral sensitivity profiles via experimental evolution, researchers have demonstrated that a single drug pair can manifest opposing interactions depending on the underlying mutation. These insights guide the design of combinatorial regimens to mitigate resistance emergence in vitro. Complementary work has shown that non-inherited, transient induction of resistance—achieved by co-administration of an antiseptic—can trigger robust collateral sensitivity to a second antibiotic in Pseudomonas aeruginosa. This transient phenotype allows elimination of resistant strains without selecting for permanent mutations, offering a novel evolutionary strategy to tackle recalcitrant infections.

Antibiotic Resistance Evolution in Bacterial Systems publication trend

The graph below shows the total number of articles in antibiotic resistance evolution in bacterial systems across all publications each year (not limited to Nature Index journals).

Technical terms

Collateral sensitivity: Increased susceptibility to one antibiotic as a trade-off of resistance to another.

Cross-resistance: Concurrent resistance to multiple antibiotics arising from a single genetic change.

Efflux pump: Membrane transporter that expels antibiotics, reducing intracellular drug concentration.

Biofilm: Structured bacterial community embedded in a self-produced extracellular matrix.

References

1. Systematic mapping of antibiotic cross-resistance and collateral sensitivity with chemical genetics. Nature Microbiology (2024).
2. Tackling antibiotic resistance by inducing transient and robust collateral sensitivity. Nature Communications (2023).
3. Bacterial evolution of antibiotic hypersensitivity. Molecular Systems Biology (2013).
4. Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution. Current Opinion in Microbiology (2015).
5. Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle. eLife (2019).