New Antibiotic Lariocidin From Backyard Soil Bacteria Attacks a New Site on the Ribosome

Researchers at the David Braley Centre for Antibiotic Discovery at McMaster University in Canada reported lariocidin, a new antibiotic made by the soil bacterium Paenibacillus sp. M2. Lariocidin belongs to the lasso peptides, a group of ribosomally synthesized and post-translationally modified peptides (RiPPs). It is a molecule whose structure is held firmly in a lasso shape, with the tail threaded through a ring, and it is the first lasso peptide that targets the ribosome.

Interacting with 16S rRNA and tRNA to disrupt protein synthesis

The strain came from soil in the backyard of a home in Hamilton, Canada, and the researchers cultured it for about a year so as not to miss slow-growing microbes. Structural, genetic and biochemical analyses showed that lariocidin binds a unique site on the small ribosomal subunit and interacts with 16S ribosomal RNA and aminoacyl-tRNA, blocking translocation and causing translation errors. It was not affected by common resistance mechanisms, the frequency of spontaneous resistance was low, and no toxicity to human cells was observed. It also showed a strong effect in a mouse model of Acinetobacter baumannii infection.

With both a new chemical scaffold and a new mechanism of action, it could open a new route to developing protein synthesis inhibitors. However, the results are at the cell and animal level, and a method for large-scale production and safety evaluation in people remain to be done.