A protein that helps fruit flies sleep also produces short peptides that kill bacteria in an unusual way. Rather than puncturing the bacterial membrane, as most germ-killing peptides do, they slip inside and interfere with the machinery that builds proteins. The work was published in Nature Communications on 29 October.
In laboratory tests the peptides worked against a wide range of microbes, including antibiotic-resistant strains. It is all lab work so far, but the mechanism differs from the membrane-puncturing action of most germ-killing peptides.
A sleep gene with an immune job
Nemuri, named after the Japanese word for sleep, was identified by a team led by Amita Sehgal at the University of Pennsylvania and reported in the journal Science in 2019. Flies with extra Nemuri slept roughly 17 to 20 hours a day, against about 11 for typical flies, and they survived infections better. Nemuri levels rose when flies were sick or deprived of sleep, and the protein could kill microbes on its own.
That work suggested that the fly's need for sleep and its immune defences are closely linked. The new study asks what Nemuri actually does to bacteria.
Cut into short peptides
The researchers found that Nemuri is cut into short peptides rich in two amino acids, arginine and glycine. It is these fragments that do the killing. Nemuri is known to drive sleep, particularly when a fly is fighting an infection.
A different way to kill bacteria
Most germ-killing peptides work by punching holes in the bacterial membrane. The Nemuri peptides do not. They enter the bacterium and gather where the ribosomes are, the structures that build proteins.
There, the ribosomes clump together and slow down, and protein production stalls. A bacterium that cannot make proteins cannot grow.
Tested against resistant strains
In lab tests the peptides worked against a wide range of microbes, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), two bacteria that are hard to treat because they resist common antibiotics. The peptides were mostly gentle on fly and mammalian cells, which is important for any compound that might one day be developed further.
How early this is
All of the evidence so far comes from laboratory experiments. Whether the peptides work in an infected animal, how they could be delivered and whether bacteria can become resistant to them are questions for later studies.