Caring for the sick, valuing the community more than just oneself and excellence in medical therapeutics have been key to surviving innumerable challenges we’ve faced as a race.
Historically, if we did not practice quarantine protocols to limit the spread of infection or provide effective medical help to patients, and develop novel therapeutics, it’s hard to imagine where we would be as a species – or if we would still remain at this point.
Healing our sick and isolating ourselves during illnesses may seem like practices exclusive to humans but let me tell you a tale about a type of ant – Meganopera analis, and how these small animals evolved social behaviors to prevent the spread of lethal infections, and also produce novel anti-microbials to treat their infected ones.
This story may serve as inspiration to us in developing novel antimicrobial therapeutics, as we face a constant threat of infections that are super-resistant to current antimicrobial treatments.
The story begins with Erik Frank, at the University of Würzburg. He is an expert on how animal behavioral patterns are intertwined with ecology and evolution. His group has been studying Meganopera analis ants for quite some time. This story is built on three seminal research articles Dr. Frank and his colleagues published since 2017.
Meganopera analis are a species of ants widely found in sub-Saharan Africa – more specifically, in the region spanning 120N to 250S. Remarkably, these ants are specialized predators of termites.
Here is how the hunting expedition goes. A scout M. analis ant brings news of a termite colony nearby – sometimes even 50 meters away from the nest. And the scout then initiates the hunting campaign.
The hunting pack comprises of 200,000-500,000 Meganopera analis ants, consisting of both large ants, called majors, and smaller ones, called minors.
The majors break down the soil layer protecting the termite colony, and the minor ants rush in through the cracks and ambush the termites residing inside. Afterward, the majors collect the dead termites and carry them to their nest.
There is, however, a very interesting aspect in this predator-prey relationship. Unlike the common predator-prey relationships that we’ve grown up hearing about, the prey termite strongly fights its predator, severely injuring, and often, killing Meganopera analis ants.
The ants who survive the hunt return to the nest pretty battered. But, in this context, there is something remarkable in these ants’ behavior – which Erik Frank reported in his 2017 article. Frank’s team discovered that after a raid, the fit ants carried their injured comrades back to the nest. Even the ones who sustained severe injuries, such as losing a leg or antenna, were safely carried back to the nest.
This unique behavioral trait of social responsibility, rescuing injured hunters, helps maintain about a 28.7% larger colony size.
|Depicts a fit ant helping an injured ant. However, this is not M. analis.
The rescued ants also participated in future raids 95% of the time – even as quickly as an hour after being injured.
So, this type of behavioral adaptation provides benefits to the entire ant colony at large.
Even for individual ants, this behavior, where community members look after each other and ants function as a team, provides unique advantages.
The benefit is most pronounced for the injured ants. When injured ants were experimentally forced to return to the nest alone, 32% of them died. Even for healthy ones, 10% of them died when returning alone instead of as a pack.
The most frequent cause of death when ants were compelled to return alone was due to spiders preying on them. It is therefore not surprising that in a natural scenario, M. analis ants never returned alone after a hunting expedition. They were always in a team, watching each other’s back.
A major hallmark of this study is that Frank’s team showed M. analis ants were able to specifically identify and salvage injured ants back to the nest, while not bothering about both dead and healthy ones.
The research team experimentally injured some ants by removing a leg on each side of their bodies. The scientists observed that while dead ants and healthy ones were completely ignored by the healthy ants in the raid, the experimentally injured ones were identified, picked up and carried back to the nest.
The second big discovery made in this study was the mechanism of how injured ants were identified by their healthy companions.
Using gas chromatography-mass spectroscopy, the authors specifically pin-pointed two pheromones the injured M. analis ants secreted– dimethyl disulfide and dimethyl trisulfide from their mandibular glands. These pheromones were identified by the healthy ants as signals to rescue their nestmates.
As proof, the authors applied the content of mandibular glands on healthy ants. These ants, despite being uninjured, were picked up by other ants who presumed they were hurt.
Until now, we have only covered the first part of this story. But there is so much more to this that makes it all the more intriguing.
In war movies, there are the scenes where someone is really injured, and their comrades carry them to safety. But there are also the scenes where an injured soldier knows there’s no saving him. “Just go,” a soldier will say, “leave me behind. Save yourself.” It’s so iconic, it’s been spoofed even in the children’s film Toy Story.
These ants also have this kind of intelligence. The ones so seriously injured that carrying them back would be futile, behaved in a way that their comrades could interpret as “leave me behind,” and their comrades know to do just that, and focus more on the less injured ants.
This is exactly what Frank’s team reported in their following publication that came out in 2018.
They found that just like how the healthy ants were socially responsible, the injured ants also acted in the colony’s interest.
To elaborate on this, the authors reported that the slightly or moderately injured ants assumed a position resembling pupae, which seemed like a signal for their rescue.
On the other hand, the very heavily injured ants, like those who lost about five limbs in the hunt, did not behave this way. They kept waving their remaining legs constantly and kept squirming. This difference in the behavior of less injured versus heavily injured ants helped the rescuing ants selectively pick up only the ones who would likely benefit from being rescued.
So, the injured ants aided triage – fascinating, isn’t it?
What happens after this is even more remarkable. Frank’s team found that once the hurt M. analis ants were carried back to the nest, the colony nursed them back to health.
For a while, I kept you wondering how injured ants returned to a raid in as little as an hour after being brought to their nest. And this question is one of the most intriguing parts of Frank’s research.
Within the first hour of getting the injured ants back to the nest, the healthy ones licked their wounds, and this reduced mortality by 80%. When the injured ants are not treated by their nestmates, the authors reported that 90% of them succumbed within a day. Further, termites clinging onto the bodies of injured hunter ants, were also removed by these nurse ants.
But then, there was something that still baffled Frank and his team. The scientists knew that the hunting grounds of M. analis ants – termite nests, are teeming with soil microbes. Many of those are pathogens that thrive on open wounds of animals. So, the nurse ants simply licking off the dirt and soil debris from the wounds of injured ants couldn’t fully explain how the injured ants survived their wounds and reduced infection.
The research team hypothesized there must be potent antimicrobial compounds that nurse ants apply while tending the injured hunters.
So, while concluding their 2018 article – the authors also posed the next important question they wanted to pursue: how did the ant colony manage to treat and cure infections in the wounds of their injured hunters?
To answer that question, Frank had to figure out if the soil in the termite nests harbored infectious organisms. His team collected soil from the natural location where the ants hunt termites and applied it to the ants experimentally injured in the lab.
Indeed, the soil in and around termite nests was rich in pathogens. The authors found that when soil was applied to the experimental wounds, they became infected as soon as 2 hours, and the infection increased with time.
If the experimental wound was treated with sterile PBS buffer as a negative control, it did not get infected. So, the soil in the termite nests definitely would cause infections in the wounds of injured M. analis ants.
Further, microbiome analysis of ants with infected wounds identified three types of highly pathogenic bacteria – Klebsiella, Pseudomonas and Burkholderia. Of these, in the remainder of the study, the authors focused only on Pseudomonas for a few reasons.
First, Pseudomonas aeruginosa was found to grow on agar plates inoculated with soil from termite nests, bolstering the idea that wounds of M. analis ants would very likely get infected with this pathogen as the injury takes place in the environmental setting of termite nest soil particles.
Second, the other two microorganisms that grew on these agar plates – Burkholderia and the fungus Rhizopus microsporus, when applied to experimental wounds of the ants, did not cause their death.
In contrast, when even a very low inoculum of Pseudomonas aeruginosa was applied on the wounds of these ants, 93% of them died within a day and a half.
Because of these two reasons, the authors concluded that Pseudomonas aeruginosa was the primary, or at least, a very major cause of wound infections here.
The authors also filmed healthy nurse ants licking and grooming the wounds of injured ants and they would then deposit secretions from metapleural glands directly on these wounds.
Secretions from the metapleural glands of both healthy ants and injured patients would be the medicine in this case.
Metapleural gland contents inhibited Pseudomonas aeruginosa growth in laboratory cultures in LB medium by 25%.
Using proteomic analyses of secretions from metapleural glands, the authors could identify 41 proteins. Some of those were toxins with antimicrobial properties, few were very similar to proteins with known bactericidal properties – such as lysozyme.
Interestingly, 9 of those 41 proteins, including the most abundant protein in these secretions were novel. That is, these proteins were previously not known to have antibacterial properties.
These chemicals hold great promise for being explored as novel antimicrobial therapeutic compounds, especially against Pseudomonas aeruginosa, which is a notorious human pathogen with very high resistance to current antibiotics.
In this context, here are some additional significant points regarding metapleural gland secretions. First, they were deposited on infected wounds right after the injured ants were carried back into the nest, which shows that these secretions have prophylactic properties that prevent bacterial infections from being established.
Second, metapleural gland secretions were again used to treat wounds after 10-12 hours. This indicates the promise of these secretions controlling infections that have already been established for several hours.
The other big novelty of this research is that the authors showed that healthy ants in the nest could discern whether the wounds of their injured nestmates were sterile or infected.
General treatment of the wounds, as well as depositing metapleural gland secretions on them, was done more frequently when wounds were infected compared to when they were sterile.
As a mechanism for this, the authors showed that the cuticular hydrocarbons from ants with infected wounds were different from the ants with sterile wounds. And this difference in cuticular hydrocarbons between the two ant groups likely served as cues to the healthy nurse ants to differentiate between infected and sterile wounds within their colony.
Even at the level of gene expression, ants with infected wounds differed considerably from those with sterile injuries – the authors demonstrated using transcriptomic analyses.
These three recent research articles by Frank et al. present amazing discoveries that have excited scientists across multiple disciplines – ecology, animal behavior, microbiologists and drug discovery experts.
These data show that not only humans, but also animals as tiny as ants, have evolved in ways to showcase remarkable socially responsible behaviors and the extraordinary sophistication treating their wounds and fighting pathogens. All of this is inspiring for human health and science.
References
- Frank et al. 2017. Saving the injured: Rescue behavior in the termite-hunting ant Megaponera analis. Science. Vol 3, Issue 4
- Frank et al. 2018. Wound treatment and selective help in a termite-hunting ant. Proceedings of the Royal Society. https://doi.org/10.1098/rspb.2017.2457
- Frank et al. 2023. Targeted treatment of injured nestmates with antimicrobial compounds in an ant society. Nat Commun. 14:8446. doi: 10.1038/s41467-023-43885-w
