tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

Jonas Krueger, Matthias Preusse, Nicolas Oswaldo Gomez, Yannick Noah Frommeyer, Sebastian Doberenz, Anne Lorenz, Adrian Kordes, Svenja Grobe, Mathias Müsken, Daniel P Depledge, Sarah L Svensson, Siegfried Weiss, Volkhard Kaever, Andreas Pich, Cynthia M Sharma, Zoya Ignatova*, Susanne Häussler*

*Corresponding author for this work
3 Citations (Scopus)

Abstract

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 (cmnm5U34) 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.

Original languageEnglish
Article numbere2312874121
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number11
Pages (from-to)e2312874121
ISSN0027-8424
DOIs
Publication statusPublished - 12 Mar 2024

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