Needle in egg, egg in duck, duck in hare…
Scientists have found a new antibiotic in a bacterium inside a worm inside an insect larva
Alexandra "Renoire" Alekseeva, XX2 century
Gram-negative bacteria are often quite dangerous to humans. Many of the antibiotics that affect them, which are now in use, were developed in the distant 1960s. And due to the growth of antibiotic resistance, we may soon need new medications that affect different gram-negative bacteria. While some scientists are working on their synthesis, others decided to see how species that encounter the same bacteria cope with them. As a rule, they synthesize antibiotics – and we could just use them in medical practice.
Recently, scientists have drawn attention to bacteria in the microbiomes of roundworms, enteropathogenic nematodes that parasitize insects. Worms penetrate into insect larvae and secrete bacteria there. These bacteria are designed to destroy competing insects, also settled in the larva, and similar bacteria isolated by them. And among these ("enemy") bacteria, for example, there is a gram–negative bacterium E.coli - E. coli, which also inhabits our digestive tract. Most of its varieties are harmless, but some cause serious food poisoning.
Usually, the process of screening microorganisms for whether they produce potentially useful antibiotics for humans involves growing them in a Petri dish along with other pathogenic bacteria. This allows you to see whether the bacteria being screened will prevent the growth of the pathogenic population. Those species that were obtained from the intestines of the described nematodes did not stop the growth of E. coli in such an experiment. But scientists have suggested that perhaps the bacteria still secrete useful antibiotics, but not too much.
And they were right. According to the results of the experiment, concentrated extracts of cultures obtained from the intestines of nematodes did not allow the population of E. coli bacteria to grow.
It turned out that the active component of the extracts is a shorter version of the protein, a peptide chain with a length of seven amino acids. Bacteria usually do not form a peptide chain at all when grown in the laboratory, and in other conditions it forms slowly and in small quantities. Scientists called it "darobactin".
Darobactin is too large to penetrate the cells of gram-negative bacteria through the outer membrane. To find out how it works, the researchers created E.coli resistance to it (it took about a week). All resistant strains had mutations in a protein called BamA, which encodes a chaperone protein. Its function is to control that the proteins belonging to the outer membrane of the bacterium remain in their place, and to help them navigate in the right direction in space. That is, it helps to form and keep the cell membrane in working order.
As it turned out, darobactin attaches to one of the outer membrane proteins, and then binds to BamA, blocking its movement, and thereby preventing the formation of a functional outer membrane. BamA is one of two essential proteins expressed on the outer surface of gram-negative bacteria.
If the bacteria in nematodes generate such a potentially useful molecule for humans, it may be worth looking for it in other microorganisms.
Article by Imai et al. A new antibiotic selectively kills Gram-negative pathogens is published in the journal Nature.
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