tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

• 成果类型: Article
• 署名作者: Krueger, Jonas; Preusse, Matthias; Gomez, Nicolas Oswaldo; Frommeyer, Yannick Noah; Doberenz, Sebastian; Lorenz, Anne; Kordes, Adrian; Grobe, Svenja; Muesken, Mathias; Depledge, Daniel P.; Svensson, Sarah L.; Weiss, Siegfried; Kaever, Volkhard; Pich, Andreas; Sharma, Cynthia M.; Ignatova, Zoya; Haeussler, Susanne
• 署名单位: Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; Hannover Medical School; Hannover Medical School; Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; Hannover Medical School; Hannover Medical School; Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; German Center for Infection Research; University of Wurzburg; Hannover Medical School; University of Hamburg; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9352
• DOI: 10.1073/pnas.2312874121
• 发表日期: 2024-03-07
• 关键词: codon usage; translation; expression; tune; gene

摘要

The success of bacterial pathogens depends on the coordinated expression of virulence determinants. Regulatory circuits that drive pathogenesis are complex, multilayered, and incompletely understood. Here, we reveal that alterations in tRNA modifications define pathogenic phenotypes in the opportunistic pathogen Pseudomonas aeruginosa. We demonstrate that the enzymatic activity of GidA leads to the introduction of a carboxymethylaminomethyl modification in selected tRNAs. Modifications at the wobble uridine base (cmnm(5)U(34)) of the anticodon drives translation of transcripts containing rare codons. Specifically, in P. aeruginosa the presence of GidA-dependent tRNA modifications modulates expression of genes encoding virulence regulators, leading to a cellular proteomic shift toward pathogenic and well-adapted physiological states. Our approach of profiling the consequences of chemical tRNA modifications is general in concept. It provides a paradigm of how environmentally driven tRNA modifications govern gene expression programs and regulate phenotypic outcomes responsible for bacterial adaption to challenging habitats prevailing in the host niche.