Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Antimicrobials

Lassoing bacterial ribosomes

Nature Reviews Microbiology volume 23, page 335 (2025)Cite this article

Subjects

Antibiotic resistance is a global health crisis as bacterial infections are becoming harder to treat, leading to increased mortality. Therefore, there is an urgent need to develop novel antibiotics. Microorganisms produce diverse secondary metabolites that exhibit antibacterial activity, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). The peptide-encoding genes are translated by ribosomes into linear chains that are subsequently subjected to post-translational modifications. Lasso peptides are RiPPs that contain a C terminus that threads through an N-terminal isopeptide-bonded intramolecular ring, giving it the distinct, 3D ‘knotted lasso’ shape. These natural products have been shown to exhibit antibacterial activity, targeting, for example, microbial ClpP protease or RNA polymerase. In a recent study, Polikanov, Mankin, Vázquez-Laslop, Wright and colleagues report the identification of a ribosome-targeting lasso peptide, termed lariocidin (LAR), that acts on a new ribosomal binding site.

Next, the authors showed that LAR did not induce cell lysis and did not permeabilize or depolarize the bacterial membrane or disrupt cell morphology. Instead, they showed that LAR exhibits its bactericidal activity by targeting the ribosome, which has not yet been shown for any other lasso peptide. Specifically, crystal structures of ribosome-bound LAR revealed that the peptide targets the small ribosomal subunit at a site that is adjacent to the decoding centre, binding to the 16S ribosomal RNA and interacting with aminoacyl-tRNA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Microbiology http://www.nature.com/nrmicro/

    Andrea Du Toit

Authors
  1. Andrea Du Toit
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Andrea Du Toit.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du Toit, A. Lassoing bacterial ribosomes. Nat Rev Microbiol 23, 335 (2025). https://doi.org/10.1038/s41579-025-01182-x

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41579-025-01182-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing