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MiaA, a tRNA isopentenyltransferase, is well studied in model organisms, but its role in the opportunistic pathogen Pseudomonas aeruginosa remains unclear. Using LC\u2013MS, nanopore tRNA sequencing, as well as transcriptional, translational, and proteomic profiling, we mapped MiaA-dependent tRNA modifications and revealed unexpected effects of MiaA loss. Impaired translation of MiaA-sensitive codons reduced quorum-sensing-controlled virulence gene expression and attenuated pathogenicity in Galleria mellonella. Ribosome stalling at trp codons in miaA mutants overrides the attenuation-controlled repression of tryptophan biosynthesis, causing overproduction of tryptophan, along with upregulation of cognate tRNAs, thereby linking translation to global metabolic adaptation. MiaA is tightly regulated and is so central to bacterial physiology that its expression level correlates directly to virulence in clinical isolates, highlighting its role as a hub connecting translation, transcription, metabolism, and pathogenicity. These findings position MiaA as a key integrator of cellular processes critical for pathogen fitness and host interactions.<\/jats:p>","DOI":"10.1093\/nar\/gkag755","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:17:53Z","timestamp":1785323873000},"source":"Crossref","is-referenced-by-count":2,"title":["MiaA-mediated tRNA modifications couple tryptophan attenuation and changes in tRNA abundance to complex phenotypes in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2485-3724","authenticated-orcid":false,"given":"Yannick N","family":"Frommeyer","sequence":"first","affiliation":[{"name":"Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research , Hannover 30625 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38124 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Br\u00f6nstrup","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, Helmholtz Centre for Infection Research, and German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig , Braunschweig 38124 ,","place":["Germany"]},{"name":"Institute of Organic Chemistry, Leibniz University Hannover , Hannover 30167 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-019X","authenticated-orcid":false,"given":"Meina","family":"Neumann-Schaal","sequence":"additional","affiliation":[{"name":"Department of Metabolomics & Services, Leibniz Institute DSMZ\u2014German Collection of Microorganisms and Cell Cultures , Braunschweig 38124 ,","place":["Germany"]},{"name":"BRICS (Braunschweig Integrated Centre of Systems Biology) , Braunschweig 38106 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