Host norepinephrine biases codon-dependent virulence translation in EHEC

ABSTRACT Bacterial pathogens sense host-derived signals to control virulence, yet how these cues shape translation remains unclear. McShane et al. show that the host hormone norepinephrine rewires the tRNA epitranscriptome of enterohemorrhagic Escherichia coli (EHEC) O157:H7, altering wobble-position modifications and shifting decoding capacity toward A/U-ending codons (A. E. C. McShane, C.-K. Chan, R. Chen, M. S. DeMott, et al., mSystems 11:e01418-24, 2026, https://doi.org/10.1128/msystems.01418-25 ). This bias aligns with the codon architecture of the locus of enterocyte effacement (LEE), a major virulence locus, enabling selective translation of virulence genes. Multi-omic analyses link these changes in tRNA chemistry to proteome remodeling without major shifts in tRNA abundance. By coupling host hormone sensing to codon-biased translation, this work establishes the tRNA epitranscriptome as a dynamic regulator of bacterial virulence.