Insects are great at killing bacteria. Can they help us find new antibiotics?
Insects carry antimicrobial proteins that kill bacteria within minutes. Researchers are investigating if these substances can fight antibiotic-resistant bacteria
What would happen to a host organism if someone infected it with one million bacteria? A mouse or a zebrafish would most likely die of a septic shock. Humans wouldn’t fare much better either. But the immune system of an insect decimated 99% of the intruders within minutes, as researchers from the Free University of Berlin, in Germany, demonstrated in an experiment.
Like humans, insects are surrounded by microbes, viruses, bacteria, and other parasites. Thus, they are constantly under attack. Although many insects only live for a few weeks, they still need to fight off harmful germs. This includes bacteria with brief life spans. So, having an immune system is worthwhile for insects.
“They have a set of important immune effectors, some of which are similar to what we have as humans. For example, they have blood cells (hemocytes) that feed on bacteria in the bloodstream. These are very similar to human white blood cells. They also produce a range of antimicrobial substances,” says the biologist Jens Rolff, a professor at the Free University of Berlin.
Rolff leads the InsectInfect, a project with scientists from German and Swiss universities. The initiative investigates how insects defend themselves against harmful invaders. The scientists are studying the fruit fly, honeybee, beewolf, wax moth, flour beetle, and cockroach.
The project might help humans find new antibiotic treatments. And with the support of other drugs, it can recover medications that no longer work because of bacterial resistance.
Protein-like killers
Insects use multiple mechanisms to attack invading microbes. One of these strategies is through antimicrobial peptides, small protein-like molecules that have diverse ways of killing bacteria and fungi, explains Dino McMahon, a project investigator of InsectInfect. “These kill microbes much more rapidly than typical antibiotics used in human medicine,” he says.
There are several types of antimicrobial peptides, some of which are key components of an insects’ defense system.
The immune cells of these invertebrates gobble up bacteria in the bloodstream and produce toxic substances that quickly kill pathogens. “Insects have ways of telling whether they are infected, akin to the human immune system. They ramp up their immune defense to cope with surviving bacteria and to avoid a return of the infection,” explains Rolff.
During that period, the insects synthesize a cocktail of antimicrobial peptides. They release these substances into the bloodstream six to 12 hours after the infection, keeping microbes under control. This “up-regulation” lasts for at least four weeks. “It’s a very long time given that a lot of adults insects only live a few weeks”, says Rolff.
Antimicrobial peptides are “ancient weapons” and the fact that we can find them in a diverse range of animals, including humans, shows a shared evolutionary history, argues Flor Arias-Sánchez, another project investigator of InsectInfect. “We can say that they developed very early. Many years before the animal kingdom diversified. So this is a very successful strategy.”
Natural resistance against antimicrobial peptides
An interesting insect studied by the researchers is the wax moth. When it enters the pupal stage, its old gut completely dissolves, releasing microbes that can spill over into the body. In humans, this could cause a life-threatening septic shock.
But the wax moth also releases antimicrobial substances that keep the number of microbes in check. Now, the researchers want to understand if the bacteria become resistant to this antimicrobial cocktail. This is relevant because these pathogens are very common in the environment.
“There’s very little natural resistance against antimicrobial peptides produced by insects. And that’s interesting because antibiotic resistance is prevalent in the environment. Studies on ice cores, so they date back 10,000 years, find resistant genes against modern-day antibiotics,” says Rolff.
The reason is that modern-day antibiotics come from natural organisms that have been around for millions of years. It’s possible that bacteria find it more difficult to build resistance against antimicrobial peptides than antibiotics.
Another “star” of the project is the beewolf. When this insect brings dead honeybees into its nest to feed its offspring, it needs to prevent them from decomposing. So, the beewolf has developed a close relationship with bacteria that grow in its antennae.
“The beewolf has little pockets on its antenna. These produce cocktails of antibiotics that the beewolf uses to cover the bees and the brood cave. This prevents fungi and bacteria from decomposing the food or killing the offspring,” explains Rolff.
The beewolf has up to 45 different antimicrobial substances. Although studying this arsenal could help humans develop new antibiotics, understanding how antimicrobial peptides developed and avoid bacterial resistance might be more relevant.
For instance, insects discharge cocktails of different antimicrobial peptides, similar to combination therapies with several drugs (a common approach to treat tuberculosis or HIV). Finding out how insects mix these peptides will inform our understanding of combination therapies, perhaps allowing antibiotics affected by bacterial resistance to still efficiently reach their targets when included in a cocktail of other medications.
“[This] is more sustainable because it starts from avoiding resistance evolution rather than managing resistant bacteria,” says Rolff.
