A Broad Spectrum Lasso Peptide Antibiotic Targeting the Bacterial Ribosome
Lariocidin and its derivative, lariocidin B, are two lasso peptides (“biologically active molecules with a distinct structurally constrained knotted fold”) produced by Paenibacillus sp. M2. These peptides exhibit potent broad-spectrum antibacterial activity by targeting a unique site on the small ribosomal subunit. Specifically, they bind to 16S rRNA and interact with aminoacyl-tRNA, thereby disrupting ribosomal translocation and inducing miscoding during protein synthesis. This mode of action differentiates them from other ribosome-targeting antibiotics and reduces the likelihood of cross-resistance with existing drugs. Notably, lariocidins demonstrate efficacy against a variety of bacterial pathogens, including multidrug-resistant strains, and have a low propensity for inducing bacterial resistance. Unlike many conventional antibiotics, they remain effective against bacteria that have developed common resistance mechanisms. Importantly, the study reports no observed toxicity to human cells, supporting their potential for therapeutic application. This research underscores the importance of discovering novel antimicrobial compounds with unique mechanisms of action, fighting antibiotic resistance. By targeting a site on the ribosome, lariocidins offer a promising foundation for the development of next-generation antibacterial therapies.
suggested by Prof. Concepción González-Bello
Orcid: https://orcid.org/0000-0001-6439-553X