Sunday, 24 January 2021

Another Newly-Discovered Substance Shows Why Biodiversity is Important

Leaf-cutter ants
New antifungal compound from ant farms - American Chemical Society

Following close on my article a few days ago on the antibiotic found in the skin of an Australian toadlet and how this demonstrates the need to maintain a rich biodiversity if only for the resource of natural medicines yet to be discovered in nature, we have another example of an unlikely compound being found - within the nest of leaf-cutter ants.

This time, it's an antifungal compound, produced by bacteria that live on the attine ants (ants of the Atta genus of what are more commonly known as leaf-cutter ants that farm fungi on a substrate of moist chewed-up leaf matter). The ants use this antifungal compound, called attinimicin, to keep their crop and its substrate free from fungal parasites.

Leaf-cutter ant, Atta cephalotes, tending fungi growing on chewed-up leaves.
From the American Chemical Society (ACS) news release of Jan 20th, 2021:
Attine ants are farmers, and they grow fungus as food. Pseudonocardia and Streptomyces bacteria are their farmhands, producing metabolites that protect the crop from pathogens. Surprisingly, these metabolites lack common structural features across bacteria from different geographic locations, even though the ants share a common ancestor. Now, researchers report in ACS Central Science they have identified the first shared antifungal compound among many of these bacteria across Brazil. The compound could someday have medical applications.

Attine ants originated as one species at a single location in the Amazon 50 million years ago. They have evolved to 200 species that have spread their farming practices throughout South and Central America. In exchange for food, bacteria at these farms produce small molecules that hold pathogenic fungi such as Escovopsis in check. However, these molecules differ from region to region, suggesting a highly fragmented and geographically limited evolutionary history for the bacteria. Monica T. Pupo, Jon Clardy and colleagues wanted to find out if any antifungal bacterial metabolites with broader distribution had been overlooked in prior investigations.

In a study of bacteria from ant nests at multiple sites in Brazil, the team discovered that nearly two thirds of Pseudonocardia strains produced a potent antifungal agent, which they called attinimicin. This discovery marked the first report of a specialized metabolite with broad geographic distribution produced by ant-associated bacteria. While this 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 treatments that are used clinically, making it a potential drug candidate.
Incidentally, there is an interesting series of symbiotic relationships going on here. The ants and the Lepiotaceae fungi on which they feed are mutually obligate symbionts and the bacteria that keep the colony free from parasitic fungi that could destroy the fungi are also dependent on the ants. The fungi have become dependent on the ants to the extent that they no longer produce spores but rely on the ants to propagate them. Instead, they produce swollen hyphal tips (gongylidia) that grow in bundles called staphylae, specifically to feed the ants.

But it is the antifungal chemical, produced by the bacteria to destroy any fungi that might take over the leaf compost or parasitise the food fungi, while not harming the Lepiotaceae fungi themselves, that is of special interest here. As explained above, this has been shown to be effective against an infection by Candid albicans (the fungus responsible for thrush) in mice, comparable to the azole-containing compounds currently in clinical use.

Another example of the surprises to be found in nature, the products of the natural evolution laboratory, which we will lose as we reduce the biodiversity of the planet.

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