tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa

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作   者：

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 H?ussler; 

作者机构：

Center of Clinical and Experimental Infection Research;  Institute for Molecular Bacteriology; 

关键词：

pathogenicity;  tRNA modification;  epitranscriptomics;  riboseq;  translation.; 

期刊名称：

Proceedings of the National Academy of Sciences of the United States of America.

i s s n：

0027-8424

年卷期：

2024 年 121 卷 11 期

页   码：

e2312874121-e2312874121

页   码：

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 (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.