Tiny animals use stolen genes to fight infections – and could fight antibiotic resistance too
Rotifers are microscopic animals and their populations are entirely female.
A little-known group of microscopic animals has spent millions of years copying recipes for antibiotics from bacteria and using them to fight infections, we have shown in a new paper. We think this unusual defensive strategy could offer short-cuts in the race to develop antimicrobial treatments.
More than 1.2 million people worldwide are killed by drug-resistant bacteria each year. Antibiotics are used to treat serious bacterial infections. Similar drugs called antifungals treat infections caused by yeasts and moulds, which are also on the rise.
Together, these antimicrobial chemicals are essential to modern medicine, but with resistance increasing, the World Health Organisation recently warned of a pressing need for new drugs.
Like many scientists, we were concerned about antimicrobial resistance, but we didn’t think our day-to-day research had much to do with it. We spend our time looking down microscopes at tiny animals, about a hair’s breadth in size. Most people have never heard of these creatures. They have a strange name: bdelloid rotifers. Pronounced DELL-oid WROTE-if-furs, it means “crawling animals that carry wheels on their heads”. They live everywhere in the world with freshwater: in ponds, streams and lakes, even where the water sometimes dries up or freezes, like moss, soil, puddles and ice sheets.
About one in ten of their genes have been copied from different kinds of life, including bacteria, fungi and even plants. To give some idea of how out of place these genes are in animals, imagine a cat with blades of grass scattered among its fur, or a dog whose tail is a mushroom.
No other animals are known to import genes on such a scale. Earlier research found that the rotifers have been picking up DNA that doesn’t belong to them for millions of years, but a big puzzle is what they are doing with these thousands of stolen genes.
Stealing genes from other species is called horizontal gene transfer. It is common in bacteria, and while it is unusual in bigger and more complicated creatures, more and more examples are coming to light. Scientists still aren’t sure how it happens, but the transferred genes often carry out functions that give their new owner an edge in the evolutionary fight for survival.
When we exposed rotifers to a deadly fungal disease that specifically infects them, we discovered that they switched on hundreds of the stolen genes to fight the infection, far more than expected by chance.
Our next surprise was what these stolen genes are doing. The most strongly activated genes looked like instructions for antimicrobial chemicals that we didn’t think animals could make.
Most antimicrobials were not invented by humans. They are natural products made by bacteria and fungi to fight each other. Imagine an over-ripe apple lying on the ground. The first spot of mould will grow better if it can stop other microbes moving in, so it makes chemicals to kill the competition. Most fungi and bacteria have recipes in their DNA for these chemicals, and humans can sometimes harvest these chemicals or make them artificially as treatments for patients, animals and crops.
Our new study shows that bdelloid rotifers have written the antimicrobial recipes into their DNA. By tracking gene activation patterns, we watched them use one of these recipes against the fungal disease that attacks them. The animals that survived the infection were making ten times more of the recipe than the ones that died. We looked at the rotifers’ DNA, using a map made by some of our colleagues. We found 30 or 40 more chemical recipes on standby, which look different from any known antibiotics.
We think these tiny animals could be allies in the hunt for antimicrobials to tackle resistant infections. There are hundreds of species of bdelloid rotifers, and they’ve had a lot of time to copy and test out recipes that microbes have left lying around.
Most natural chemicals from microbial turf wars are poisonous to animals (like that mouldy apple). Only a few can be turned into treatments, and it’s difficult and expensive to tell which ones are safe. If rotifers are already making a chemical in their own cells, this hints that they might have adjusted or selected the recipe to be safer for other animals, perhaps including people.
Sex-starved rotifers
A big question raised by our work is why rotifers are the only animals known to adopt such extreme levels of DNA piracy. It may sound strange, but we think part of the answer is that they’re not getting enough sex.
Unlike other known animals, all bdelloid rotifers are females, with no sightings of males in the 300 years since they were discovered. Rotifer mothers lay eggs that hatch into genetic copies of themselves, without sex, sperm or fertilisation.
Copying yourself like this is a quick way to increase in numbers, but it usually comes with a big price in the longer term. Infectious diseases are always changing, as seen recently with COVID. When animals and plants have sex, their genes are shuffled into new combinations, which helps the next generation to resist diseases. Scientists think organisms that reproduce by copying themselves exactly can get in trouble, because if one individual gets infected, the disease can easily spread to all the others with the same genes.
If this thinking is right, then the sex-starved rotifers need other ways to manage diseases. If they can’t easily shuffle their own genes through sex, then taking DNA from other places might be a useful stopgap. This could explain why an unusually high number of stolen genes responded to infections.
It can take decades for a new drug to get approval from regulators and only a fraction of treatments ever make it through medical trials. However, as is often the case in biology, studying creatures that have spent millions of years grappling with similar problems can lead to surprising possibilities.
Christopher G. Wilson receives funding from the UK Natural Environment Research Council (NERC).
Reuben W. Nowell receives funding from the UK Natural Environment Research Council (NERC).
Tim Barraclough receives funding from the UK Natural Environment Research Council (NERC).