The venom of forest ants and horse ants contains numerous substances that protect the insects from pathogens. Researchers at Martin Luther University Halle-Wittenberg (MLU) and Freie Universität Berlin have succeeded for the first time in identifying and characterising these novel antimicrobial substances in the insects’ venom. These substances are peptides, small protein molecules. The study, published in the journal ‘Science Advances’, provides new insights into nest protection and the management of microbes in insect communities. At the same time, the newly discovered substances could provide fresh impetus for medical drug discovery.

Since formic acid was first isolated from Formica ants back in the seventeenth century, the venom of these ants was considered to be rather simple in its composition. It was believed that formic acid served as the principal toxin, and although findings from earlier studies suggest the presence of peptidic compounds in the venoms, these observations were largely overlooked. “In our project, we investigated a decades-old publication that received little attention in its time. The paper mentioned that these venoms also contain peptidic compounds,” says project lead and professor for pharmaceutical biology at Freie Universität Berlin’s Institute of Pharmacy, Timo Niedermeyer. “We investigated the venoms of eight geographically distant species of carpenter ants and uncovered thirty-five peptides, or formicitoxins, belonging to two gene families. The specific make-up of the formicitoxins varied from species to species, but their presence was widespread. This means that carpenter ant venom is considerably more complex than previously assumed.”

The peptides that the researchers discovered likely contribute toward the hygiene of the ants’ nest. The ants spread their venom onto the brood and the area surrounding the nest, leading the researchers to propose that the formicitoxins reinforce an external immune defense that lingers after the immediate antimicrobial effects of formic acid have lost their potency. “Some of the peptides demonstrate remarkable antifungal properties. This is particularly interesting when we consider the threat that environmental microbes and pathogens pose to social communities such as ants, as well as the increased threat of microbial resistance for human well-being,” emphasizes Dr. Simon Tragust, project lead at the Institute of Biology at Martin Luther University Halle-Wittenberg. “The Formicinae subfamily comprises over 3,700 species, meaning that there is enormous potential for the discovery of more bioactive substances.”

The results confirm that carpenter ant venom performs a range of diverse functions. The ants use their venom not only for defense, but also to disinfect their surroundings, to acidify their gut for microbial selection, and to communicate with other ants.

For their study, the researchers combined methods from the fields of biology, chemistry, and pharmacy. Using a proteotranscriptomic approach, they combined protein and RNA data taken from the venom and associated tissues to identify the individual peptides, as well as their genetic sequences. They also made use of chemical analyses, performed bioactivity assays, and synthesized their own formicitoxins. The scientists gained further insight into the structure and evolutionary history of the individual venom components through biophysical experiments, genome analyses, and computer-assisted modeling.

Thanks to its interdisciplinary approach and the examination of venom from multiple ant colonies, this study represents one of the most comprehensive comparative analyses of ant venom carried out to date.

The work was funded by the German Research Foundation, the State of Saxony-Anhalt and the Ethological Society.

Study: Koch L. et al. Beyond formic acid: Peptides in carpenter ant venoms aid in disease protection. Science Advances (2026). doi: 10.1126/sciadv.aed4078