Thiopeptide Defense by an Ant’s Bacterial Symbiont

Abstract

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 <i>Pseudonocardia</i> symbionts of the ant <i>Trachymyrmex septentrionalis</i> 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 <i>in vitro </i>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.

Pharmacological potential of ants and their symbionts – a review

“…Actinomycin isolated from a Streptomyces strain of Acromyrmex is known to have antimicrobial activity against Pseudonocardia and other strains of Streptomyces (Schoenian et al, 2011). Another thiopeptide GE37468, obtained from Pseudonocardia symbiont of the fungus‐growing ant, Trachymyrmex septentrionalis (McCook), is not only a well‐known antibiotic against Gram‐positive bacteria including human pathogens but also contributes to host defence (Stella et al, 1995; Chang et al, 2020). Other than having antimicrobial activity, few antibiotics obtained from ant endosymbionts also possess anti‐protozoan and anti‐proliferative properties.…”

Introduction to Thiopeptides: Biological Activity, Biosynthesis, and Strategies for Functional Reprogramming

“…(Figure S1), a berninamycin-like thiopeptide produced by a skin commensal Cutibacterium acnes (Christensen et al, 2016;Claesen et al, 2019), decreases the risk of colonization by pathogenic Staphylococcus species (Claesen et al, 2019). The role of thiopeptides in bacterial niche competition is not limited to human microbiomes: GE37468-producing (structure in Figure 5) symbionts of the ant Trachymyrmex septentrionalis utilize it to antagonize their most likely competitors, other ant-associated bacteria (Chang et al, 2020).…”

Bacterial Associates of a Desert Specialist Fungus-Growing Ant Antagonize Competitors with a Nocamycin Analog

“…10 In a population of the North American ant Trachymyrmex septentrionalis, Pseudonocardia antagonize competitors using the thiopeptide antibiotic GE37468. 11 Actinobacteria other than Pseudonocardia have been detected on the cuticle of fungus-growing ants in both culture-dependent and sequencing-dependent studies, and it remains debated whether these additional bacteria are transient or instead are maintained by the ants as part of a more complex cuticular microbiome. 12 Competition is expected when multiple bacterial strains co-occur in an ant population, and conceptual frameworks have been developed for such bacteria−bacteria competition in the context of fungusgrowing ants.…”