Discovery of new secondary metabolites mediating insect-microorganism symbioses

Host-microbe symbioses play a critical role in the evolution of biological diversity and complexity. One of the best-known examples is the quadripartite symbiosis involving fungus-growing ants. These ants (Attini, Formicidae) cultivate a fungus as their primary food source. Successful fungal cultivation by fungus-growing ants is threatened by an antagonistic fungus (Escovopsis sp.), which is a specialized parasite of the ants' fungal garden. Bioassays and in vivo infection experiments have shown that the ants use symbiotic actinomycetes (Pseudonocardia sp.) to inhibit the antagonistic fungus [1]. We have recently identified another example of an insect employing actinomycetous bacteria to mediate their antagonistic and beneficial symbiont community, involving the southern pine beetle (Dendroctonus frontalis), its mutualistic fungus (Entomocorticium sp. A), an antagonistic fungus (Ophiostoma minus), and a bacterial symbiont (Streptomyces sp. SPB74). In a basal species of fungus-growing ants (Apterostigma dentigerum), investigation of bacterial secondary metabolites revealed that a previously unknown macrocyclic depsipeptide, bearing three piperazic acids and β-hydroxy leucine as well as a polyketide-derived moiety, inhibits the relevant antagonistic fungus, Escovopsis sp. We also discovered that a novel polyene peroxide, with a conjugated heptaene and a 1,2-dioxolane endoperoxide functionality, selectively inhibits the antagonistic fungus, Ophiostoma minus, in the southern pine beetle system where its mutualistic fungus, Entomocorticium sp. A, is resistant to this key molecule. These results indicate that studying insect-microorganism symbiotic systems and identifying their small molecule mediators provides an effective search strategy for new natural products with pharmaceutical potential.

References: 1. Currie, C. R. et al. (1999) Nature 398:701.