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Here, we identified features of transfer RNA (tRNA) reprogramming and codon-biased translation that play a role in this infectious process. Multivariate statistical analysis of genome-wide codon usage patterns revealed five gene clusters with unique codon biases, with one cluster containing all Locus of Enterocyte Effacement virulence genes that are all strongly biased for A\/U-ending codons. EHEC cultures were then exposed to a norepinephrine gradient to induce type III secretion, as well as chemotaxis and flagellar motility, followed by a multi-omic interrogation of changes in tRNA modifications, tRNA abundance, and the proteome. We observed altered levels of multiple tRNA wobble modifications involved in G\/C- versus A\/U-ending codon recognition and a corresponding shift in the proteome toward genes enriched in A\/U-ending codons. Our studies suggest EHEC can alter its tRNA pool in response to cues from the host, fine-tuning translational efficiency of its virulence program.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Regulation of microbial physiology and virulence during environmental changes has typically been ascribed to transcriptional mechanisms. Using convergent multi-omic technologies, we have discovered mechanisms of translational regulation of gene expression that regulate cell phenotype. Here, we applied these technologies to define mechanisms of translational regulation in the\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        O157:H7 response to norepinephrine exposure known to induce virulence.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01418-25","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:00:40Z","timestamp":1776862840000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Enterohemorrhagic\n                    <i>Escherichia coli<\/i>\n                    O157:H7 responds to norepinephrine gradients by tRNA reprogramming and codon-biased translation of virulence genes"],"prefix":"10.1128","volume":"11","author":[{"given":"Abigail 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