Copper stress upregulates oxidative stress response, histidine production and iron acquisition genes in E. coli

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ID: 328673
2026
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Abstract
Abstract Copper is widely used as a fast-acting antimicrobial, yet the strategies that allow bacteria to survive copper stress remain incompletely understood. Here, we characterize the transcriptional responses of Escherichia coli MG1655 to excess ionic copper using RNA sequencing and a genome-wide GFP-based promoter library. We applied 2 mM copper, which slows growth, and 8 mM copper, a near-lethal concentration. RNA-seq revealed extensive transcriptome remodeling, with 487 genes upregulated at 2 mM and 364 at 8 mM. Both concentrations strongly induced canonical copper-responsive systems, oxidative stress defenses, histidine biosynthesis, and multiple iron acquisition pathways – including enterobactin biosynthesis and transport – despite external iron failing to reduce copper toxicity. At 2 mM copper, additional pathways were activated, including heat-shock and protein-folding functions as well as lipid A, methionine and arginine biosynthesis. Copper exposure also repressed large gene sets: 486 genes at 2 mM, enriched for biofilm formation and pH elevation, and 217 genes at 8 mM, enriched for anaerobic metabolism. In contrast to the robust RNA-seq results, we investigated the Horizon Discovery E. coli genome-wide GFP based promoter library as an alternative screening tool. However, in our experiments it showed low signal-to-noise ratios, limiting its suitability for large scale gene expression screening.
Reference Key
openalex_W7213462562 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hanna Ainelo, Karola Joearu, Andres Ainelo, Angela Ivask
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Journal FEMS Microbes
Year 2026
DOI
10.1093/femsmc/xtag050
URL
https://doi.org/10.1093/femsmc/xtag050
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