Attine ants grow fungus as food. Pseudonocardia and Streptomyces bacteria produce metabolites that protect the crop pathogens. However, these metabolites lack common structural features across bacteria from different geographic locations event though the ants share a common ancestor.

Now scientists report in ACS Central ScienceSpecialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis,” that they have identified the first shared antifungal compound, which could eventually have medical applications, among many of the bacteria across Brazil.

“Here we report the structure of attinimicin, its putative biosynthetic gene cluster, and the evolutionary relationship between attinimicin and two related peptides, oxachelin A and cahuitamycin A. All three nonribosomal peptides are structural isomers with different primary peptide sequences,” write the investigators.

“Attinimicin shows iron-dependent antifungal activity against specific environmental fungal parasites but no activity against the fungal cultivar. Attinimicin showed potent in vivo activity in a mouse Candida albicans infection model comparable to clinically used azole-containing antifungals. In situ detection of attinimicin in both ant nests and on worker ants supports an ecological role for attinimicin in protecting the fungal cultivar from pathogens.”

“The geographic spread of the attinimicin biosynthetic gene cluster in Brazilian Pseudonocardia spp. marks attinimicin as the first specialized metabolite from ant-associated bacteria with broad geographic distribution.”

Monica T. Pupo, PhD, and Jon Clardy, PhD, both associated with the University of São Paulo, and colleagues studied ant nests at multiple sites.

The team discovered that almost two thirds of Pseudonocardia strains produced a potent antifungal agent they called attinimicin. The discovery marked the first report of a specialized metabolite with broad geographic distribution produced by ant-associated bacteria. While the metabolite was safe for the fungal crop it inhibited growth of fungal parasites, though unlike many antibiotics, only in the absence of iron.

It was also effective in fighting a Candida albicans infection in mice, comparable to azole-containing antifungal therapies that are used clinically, making is a potential drug candidate.

The researchers worked out attinimicin’s structure and studied its evolutionary relationship to two similar bacterial peptides produced by Streptomyces (oxachelin A and cahuitamycin A.) The results suggest the associated genes in the two types of bacteria came from a common ancestor.

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