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Researchers identified a previously uncharacterized ribonuclease in Pseudomonas aeruginosa, named Ribocin, which cleaves eukaryotic ribosomal RNA at helix 69, a conserved structural element critical for ribosome function and translation. This cleavage was demonstrated to inhibit protein synthesis in C. elegans, mammalian cells, and rabbit reticulocyte lysates, and Ribocin was shown to contribute to bacterial virulence independently of the known virulence factor Exotoxin A. The findings establish targeted rRNA cleavage as a distinct bacterial mechanism for disrupting host translation during infection.
Why it matters
Understanding how P. aeruginosa disables host protein synthesis at the ribosomal level may inform the development of new therapeutic strategies against this opportunistic pathogen, which poses a serious threat particularly to immunocompromised patients and those with cystic fibrosis.
by Alejandro Vasquez-Rifo, Denis Susorov, Emily H. Sholi, Gabriel Demo, Yasaman Jami, Jihui Sha, James A. Wohlschlegel, Andrei Korostelev, Victor Ambros
Pseudomonas aeruginosa employs host translation inhibition as a virulence-enhancing strategy. We previously showed that the bacterium induces cleavage of Caenorhabditis elegans large ribosomal RNA at helix 69 (H69), part of a central intersubunit bridge and the ribosomal decoding center. In this study, we demonstrate that a previously uncharacterized ribonuclease, Ribocin, is necessary and sufficient for H69 cleavage. Recombinant Ribocin cuts H69 in worm and mammalian ribosomes, indicating that H69 cleavage by P. aeruginosa is phylogenetically conserved. In worms, mammalian cells, and rabbit reticulocyte lysates, H69 cleavage results in translation inhibition. Furthermore, Ribocin contributes to bacterial virulence toward C. elegans, triggers a major host response to translation inhibition, and operates in parallel with Exotoxin A-mediated translation inhibition. These findings unveil the first known nuclease that cleaves eukaryotic ribosomes at H69 and expand the understanding of host translation-inhibition by establishing targeted rRNA cleavage as a mechanism of host attack.