Thiopeptide Defense by an Ant’s Bacterial Symbiont

Fungus-growing ants and their bacterial symbionts have emerged as a model animal-microbe symbiosis and an ideal system for understanding antibiotic deployment in an ecological context. We found that Pseudonocardia symbionts of the ant Trachymyrmex septentrionalis have strong antibiotic activity against their most likely competitors: other strains of ant-associated bacteria. Activity-guided fractionation revealed the defensive molecule produced by these bacteria to be the thiopeptide antibiotic GE37468. Here we assign an ecological role – host-associated niche defense – for this antibiotic, previously identified in a biochemical screen and known only for its in vitro activity against clinically-relevant pathogens. Genomic analysis uncovered a split biosynthetic gene cluster for this molecule and suggests that these symbionts acquired it from soil bacteria. Similar thiopeptide antibiotics have recently been ascribed host-associated niche defense roles, and the function of GE37468 in this insect niche intriguingly parallels thiopeptide defense in the human microbiome. Molecular defenses from animal-associated microbes may have particular promise as therapeutics, and indeed thiopeptide antibiotics with high structural similarity to GE37468 are already under clinical investigation.