UMMS Affiliation

Program in Molecular Medicine

Publication Date

2020-12-01

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Biology | Developmental Biology | Pathogenic Microbiology

Abstract

Pathogens such as Pseudomonas aeruginosa advantageously modify animal host physiology, for example, by inhibiting host protein synthesis. Translational inhibition of insects and mammalian hosts by P. aeruginosa utilizes the well-known exotoxin A effector. However, for the infection of Caenorhabditis elegans by P. aeruginosa, the precise pathways and mechanism(s) of translational inhibition are not well understood. We found that upon exposure to P. aeruginosa PA14, C. elegans undergoes a rapid loss of intact ribosomes accompanied by the accumulation of ribosomes cleaved at helix 69 (H69) of the 26S ribosomal RNA (rRNA), a key part of ribosome decoding center. H69 cleavage is elicited by certain virulent P. aeruginosa isolates in a quorum sensing (QS)-dependent manner and independently of exotoxin A-mediated translational repression. H69 cleavage is antagonized by the 3 major host defense pathways defined by the pmk-1, fshr-1, and zip-2 genes. The level of H69 cleavage increases with the bacterial exposure time, and it is predominantly localized in the worm's intestinal tissue. Genetic and genomic analysis suggests that H69 cleavage leads to the activation of the worm's zip-2-mediated defense response pathway, consistent with translational inhibition. Taken together, our observations suggest that P. aeruginosa deploys a virulence mechanism to induce ribosome degradation and H69 cleavage of host ribosomes. In this manner, P. aeruginosa would impair host translation and block antibacterial responses.

Keywords

Pseudomonas aeruginosa, Ribosomal RNA, Caenorhabditis elegans, Ribosomes, Virulence factors

Rights and Permissions

Copyright: © 2020 Vasquez-Rifo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.1371/journal.pbio.3000969

Source

Vasquez-Rifo A, Ricci EP, Ambros V. Pseudomonas aeruginosa cleaves the decoding center of Caenorhabditis elegans ribosomes. PLoS Biol. 2020 Dec 1;18(12):e3000969. doi: 10.1371/journal.pbio.3000969. PMID: 33259473; PMCID: PMC7707567. View article on publisher's site

Journal/Book/Conference Title

PLoS biology

Related Resources

View article in PubMed

PubMed ID

33259473

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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