Lariocidin: A Novel Lasso Peptide Antibiotic Targeting Bacterial Ribosomes

:collision: Lariocidin (LAR) is a lasso peptide antibiotic discovered from a soil Paenibacillus strain. It represents a new scaffold of ribosomally-synthesized peptides with potent, broad-spectrum antibacterial activity.

:right_arrow: M.O.A: Data shows that lariocidin binds to a unique site on the small (30S) ribosomal subunit where it contacts 16S rRNA and incoming aminoacyl-tRNA. This interaction inhibits translocation and induces miscoding, blocking protein synthesis by a mode not previously exploited by marketed antibiotics. Because it targets a novel ribosomal site, common resistance mechanisms do not readily inactivate it.

:right_arrow: R.O.A: Animal work in the discovery report used parenteral dosing.

:pencil: Pre Clinical Studies Results:

  • In-Vitro: Minimum inhibitory activity (MIC) against a range of Gram-negative and Gram-positive pathogens like Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus etc. is found potent.
  • Cytotoxicity: No detectable toxicity to human cells in initial assays and a low propensity for selection of spontaneous resistant mutants in laboratory tests.
  • In vivo (animal): Demonstrated potent efficacy in a mouse neutropenic-thigh infection model of multidrug-resistant A. baumannii, with significant reduction in bacterial burden and improved survival compared with controls.

:warning: Clinical Trials: As of evidence, lariocidin is still in its preclinical stage.

MBH/PS

2 Likes

Lariocidin combats microorganisms like never before! A novel ribosomal target indicates a new strategy to fight infections and overcome resistance.

2 Likes