Ant venom: not just formic acid

Formicine ants are famous for producing formic acid, but Lukas Koch and colleagues found that their venom contains much more than previously assumed. In a recent paper titled “Beyond formic acid: Peptides in carpenter ant venoms aid in disease protection” and published in Science Advances, an interdisciplinary research team investigated the venom of Camponotus nicobarensis. They found peptides and other compounds that appear to help protect ants and brood against fungal pathogens. MNB interviewed the authors Lukas Koch, Simon Tragust and Timo Niedermayer about their findings, the value of interdisciplinary collaboration and the promising future of ant venom research.

Edited by Elia Guariento and Salvatore Brunetti

MNB: Could you tell us a bit about yourself?

ST: Sure. I consider myself an organismal biologist with a keen interest in how social insects navigate their microbial environment.

LK: I’m a biochemist by training, currently working as a doctoral research assistant at Freie Universität Berlin. My research interests lie in peptide and natural products chemistry. I’m interested in the structural diversity of bioactive molecules and the challenge of characterising them.

TN: I am a pharmacist and professor for Pharmaceutical Biology at Freie Universität Berlin. Like Lukas, I am interested in the chemicals produced by living organisms – bacteria, fungi, plants, and animals – especially their chemistry and their biological activity, which make them interesting as leads for drug development or as biochemical tools.

MNB: Could you briefly outline your research on Koch et al. “Beyond formic acid: Peptides in carpenter ant venoms aid in disease protection” in layperson’s terms?

ST/LK/TN: Our study describes the discovery, structure, evolutionary history and bioactivity of peptides, short chains of amino acids, in the highly acidic venoms of formicine ants. Formicine ants are well known for producing formic acid, and their venom was long assumed to consist of little else. We found that the venom also contains peptides that appear to help the ants ward off fungal pathogens, so the picture turns out to be considerably more complex than the textbook version. To study the venom composition and functions, we used an interdisciplinary approach combining methods and expertise from biology, chemistry, and pharmacy.

MNB: What is the take-home message of your work?

ST/LK/TN: In biology, things are seldom as clear-cut as they appear or as textbooks tell us: Formicine ant venoms are more complex than previously appreciated. Beyond formic acid, they contain peptides, lipids, and proteins, making them as complex as venoms of many stinging ant species. More broadly, our work is a reminder that seemingly well-understood systems can still hold genuine surprises.

MNB: What was your motivation for this study?

ST: To do something new.

LK: It was a good opportunity to combine my background in peptide chemistry with an interest in ants I’ve had since I was a teenager – and there was very little literature on formicine venom composition beyond formic acid, so we were essentially starting from a blank canvas.

TN: When I had a chat with Simon and he made me aware of the lack of knowledge about formicine ant venom chemistry, I was immediately interested to work on this together with him. I love following up on ancient papers that have largely been ignored for decades, using modern analytical methods to solve questions that could not be answered at the time they came up.

MNB: What was the biggest obstacle you had to overcome in this project?

ST: Actually, I don’t think that there were big obstacles, but Lukas, the first author, might be of a different opinion.

LK: Most things went quite smoothly! The trickiest part was probably that we were navigating uncharted territory and had to adjust the trajectory of the project as we progressed. The paper is also an account of the detours we took, for instance, analyzing the metal contents of the venoms after we found strong potassium-related signals using MALDI-MS.

TN: We were in the lucky position that Lukas was funded by a scholarship, but we did not have any funding for consumables or external services. Simon and I wrote two proposals to cover these costs, but both were rejected – for reasons I still don’t really understand… 🙂

MNB: Do you have any tips for others who are interested in doing related research?

ST: Finding the right people to work with and in whom you can put trust is key for endeavours beyond your area of expertise.

LK: Seek out collaborations whenever you hit a question you can’t answer alone, and invest real effort in understanding what your partners actually do. Only by finding a common language between disciplines you stop exchanging data and start producing answers.

TN: I completely agree with Simon and Lukas – doing interdisciplinary research is really rewarding, and adding biological meaning to our chemical analyses often adds greatly to the stories one can tell in the end. Also, intrinsic motivation is key for success – look for a project you really burn for. We were lucky to find Lukas for this project – we could not have done it without his dedication!

MNB: Where do you see the future for this particular field of ant research?

ST: Given the multitude of exocrine secretions in ants and other social insects that have not been investigated with state-of-the-art methods and technology, the field is wide open for discovery.

LK: Growing genome availability and technological progress will make multi-omic approaches increasingly powerful for characterising venom complexity and evolutionary history. The challenge will be to ground that data in an organismal context. Understanding what a molecule actually does in the life of an ant is ultimately more interesting than knowing it exists.

ST/LK/TN: Looking at the field from a pharmaceutical perspective, I think that not only the function of the metabolites for the producing ants themselves is interesting, but also their potential applicability in medicine. Studying under-researched organisms always increases the chances to find novel compounds with interesting properties.