Untangling Antibiotic Resistance with Lariocidin

A group of researchers recently identified a brand-new type of antibiotic called lariocidin (LAR). It’s produced by a bacterium called Paenibacillus, that lives around the soil of plant roots. The molecule has a distinctive lasso peptide structure, meaning part of the peptide loops around and threads through itself, creating a tight, stable knotted shape.

What makes lariocidin especially interesting is how it stops bacteria from growing. LAR is the first known antibiotic of its kind to bind to a specific site on the small ribosomal subunit, interacting with both 16S rRNA and aminoacyl-tRNA. In doing so, it disrupts ribosome translation and causes miscoding as proteins are being built. Preliminary tests have shown strong activity against both Gram-positive and Gram-negative bacteria, along with promising in vivo results in mouse models.

LAR also doesn’t seem to be impacted by several common resistance mechanisms, including natural lasso-peptide–cutting enzymes or typical ribosomal mutations. When researchers tried to force bacteria to evolve resistance by exposing them to high concentrations of LAR, they found far fewer resistant mutants compared to other antibiotics. This suggests that bacteria may need multiple mutations at once in order to resist it.

Overall, LAR’s structure and ability to block protein production give scientists a new scaffold to explore for antibiotic development. Its stability, low resistance risk, and lack of toxicity toward human cells make it a very promising candidate for future drug research.