Low-Dose Antibiotics Wake Bacteria's 'Sleeping Genes' and Reveal 9 New Natural Products

Researchers in the chemistry department at Princeton University in the United States presented a screening method that uses antibiotic hormesis to find bacteria's hidden natural products. Microbial genomes hold many natural product biosynthetic gene clusters, but most are barely expressed under standard laboratory culture conditions and remain so-called cryptic metabolites.

Stimulating 9 bacterial species with a library of clinical antibiotics

Hormesis is the phenomenon in which a substance that inhibits growth at high doses stimulates other responses at low doses. The researchers gathered every clinical antibiotic available into their own library and ran both high-dose growth inhibition tests and low-dose metabolite stimulation tests on 9 phylogenetically diverse bacterial species. Production of cryptic metabolites was induced in every strain tested. They fermented 4 of the strains at scale and analysed their metabolomes, finding 8 compounds that were already known but newly identified in those strains and 9 natural products with new structures.

According to the researchers, the method is simple and easy to scale up, so it can be used as a platform for finding drug candidates. That low-dose antibiotics consistently act as signals that regulate microbial metabolism also suggests ecological significance. However, the pharmacological activity and therapeutic potential of the newly found compounds need further verification.