We were really lucky. We saw all sorts of creatures from coatis and kinkajous (possibly the cutest animal ever!) to red-eyed tree frogs, massive cane toads, scarlet macaws and even the resplendent quetzal.
Well the particular Leafcutter ants at La Selva Biological Station, a protected area of rainforest dedicated to research and study of this special ecosystem, and a place I went on a guided walk with a ranger, has studied these ants and found some new microbiology! La Selva is a special (and very wet) place in Sarapiqui, Costa Rica.
Leafcutter ants don’t actually eat the leaves they collect, they are farmers. They use the leaves to produce compost; they use the compost to “feed” and grow a fungus which they then eat. Did you know there are 47 different species of Leafcutter ant and all eat fungi from the Lepiotaceae family (each species of ant eats a slightly different type of fungus)? OK so what has this fungus got to do with clinical microbiology…honest it’s explained a little later! …
In order for the ants to farm and grow fungi successfully, it is really important they do not bring back bits of leaf accidentally “contaminated” with a different fungus which might damage their crop. This is especially true if the leaf is contaminated with the fungi Escovopsis spp., which lives and feeds on other fungi! The ants therefore need some way of cleaning the leaves and preventing this contamination from happening. In order to protect their crop the Leafcutter ants are symbiotically colonised with a Pseudonocardia spp. bacterium. This bacterium produces an antifungal which kills the Escovopsis spp., how cool is that!? This previously unknown antifungal was discovered at La Selva in Costa Rica and they called it Selvamicin...
Apparently the researchers collected the Pseudonocardia spp. bacterium from two adjacent nests of Leafcutter ants and “screened them” for antimicrobial compounds. Fascinating, I would love to know how they did this… how on earth do you swab a leafcutter ant? I can imagine having to chase it around the laboratory without accidentally squishing it with the swab, or maybe they have a “swab trap” like a camera trap…? Who knows??
Does this have any clinical relevance?
Yes! Selvamicin is a polyene antifungal, similar to Amphotericin B and Nystatin which we already use in clinical microbiology. Selvamicin has been shown to be active against Candida spp., Saccharomyces spp. and Aspergillus fumigatus. I presume it has no activity against the Lepiotaceae spp. which the ants are trying to grow; as clearly that would be a poor evolutionary step!
Although Selvamicin is a polyene antifungal, it is different to Amphotericin B and Nystatin in some important areas, especially it’s mechanism of action and its water solubility.
Mechanism of Action
So far we don’t yet know how Selvamicin works; we do know it is different to the currently used polyenes. Whereas Amphotericin B and Nystatin interact with ergosterol in the fungal cell membrane, essentially behaving like a detergent by making holes in the membrane, Selvamicin does not. This is important because it means Selvamicin won’t be affected by mechanisms that lead to resistance through changes in ergosterol synthesis.
Neither Amphotericin B nor Nystatin is available orally because of their poor solubility; this means they cannot be absorbed from the gut. Selvamicin however has a 300-fold better solubility; so it probably will be orally bioavailable. This could be a game changer because currently only the azole antifungals are available orally. Therefore at the moment, if a patient has an azole resistant infection, they would have to be admitted for intravenous treatment as no other oral agent is available; a second class of oral antifungal would be brilliant.
And another thing…
Something slightly peculiar that the researchers at La Selva observed with Selvamicin is that in one of the Leafcutter ant nests the genes for producing Selvamicin were part of the chromosome of the Pseudonocardia spp. whereas in the other nest the genes were in a plasmid (mobile genetic element). The fact that the gene is found in both a chromosome and a plasmid suggests to me that it is part of a mobile genetic element that can move between bacteria. New genes can be added to either chromosomes or plasmids through the action of transposons which are genetic sequences that “help” small segments of genes move between larger sequences of genes. It also implies that Selvamicin production wasn’t originally part of Pseudonocardia spp. genetics and that it has been acquired from somewhere else.
So if it was not part of the original genetics where did it come from? Are there other, as of yet, untapped resource of antimicrobials out there in the jungle? I think I need a sabbatical to go and play in the rainforest, I mean “undertake some serious important research” … of course!
NB Thanks to the Editor Chief in Charge (aka my wife) for her tremendous efforts to get MNB to its 3rd edition…