Transcriptomic and proteomic profiling of antibiotic resistance gene expression in bacteria exposed to uranium stress
Uranium (U) exerts combined chemical and radiological toxicity to bacteria, yet its regulatory impact on the expression of antibiotic resistance genes (ARGs) remains poorly understood. In this study, we profiled the transcriptomic and proteomic responses of Gram-negative Escherichia coli and Gram-positive Bacillus subtilis under exposure to U at environmentally relevant concentrations. At 0.05 and 5 mg/L U, E. coli exhibited 6 (4 up, 2 down) and 80 (29 up, 51 down) differentially expressed genes (DEGs), respectively, while B. subtilis showed 566 (193 up, 373 down) and 432 (125 up, 307 down) DEGs. Each bacterium adopted distinct strategies for modulating the expression of ARGs, including those encoding efflux pumps. E. coli coordinately upregulated toxin–antitoxin modules, quorum‑sensing machinery, and two‑component systems, shifting to a tolerance state. Conversely, B. subtilis repressed these systems transcriptionally while reinforcing cell wall‑associated two‑component pathways at the protein level, thereby maintaining active growth and repair. Together, our findings reveal the molecular mechanisms through which radioactive heavy metals may promote the evolution of antibiotic resistance, providing a framework for assessing resistance risks in U‑contaminated environments.

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