The antibiotics are slowly becoming scarce: worldwide resistance against the former miracle weapon of medicine is increasing. With an innovative approach, a team around Zongquian Wang discovered two new antibiotics. In the specialist magazine "Science", the experts from Rockefeller University in New York describe their latest find: the substance "Cilagicin", which is supposed to act against some resistant germs. "The study shows the importance and performance of the" Genome Mining "in the discovery of new active ingredients," says microbiologist Yvonne Mast from the Leibniz Institute DSMZ in Braunschweig, which was not involved in the study.
Most antibiotics come from fungi or bacteria themselves. These produce the means to assert themselves against competing tribes. The genetic blueprint is stored in biosynthesis gene clusters. Under laboratory conditions, however, it is difficult to induce the microorganisms to produce the antibiotic of a specific gene cluster and to isolate it afterwards.
Therefore, the researchers from Rockefeller University used the "genome mining", which in German means something like "genome flakes". First, they searched for genetic sequences in the genome of around 10,000 bacterial strains that provide the blueprint for lipopeptides. This can be suitable remedies for bacterial infections because they have a variety of mechanisms of action that are directed against various pathogens. The biologists from the United States through the United States according to genetic clusters with instructions for the development of lipopeptides that are evolutionarily not related to common antibiotics. They found what they were looking for in a small life that farmers normally use to stimulate root formation: the bacterium paenibacillus mucilaginosus.
Using bioinformatics and synthetic biology to achieve the goal
Instead of growing up to the microorganisms and gaining the medication through a complex substance cleaning, the researchers with algorithms of bioinformatics predict how the substance could look like. Then they rebuilt them with chemical processes. The scientists christened the newly discovered funds "Cilagicin". According to Mast, which also researches new antibiotics, the special feature of the study is in the same approach.
Studies in the petri dish and on mice show that numerous bacteria can be combated with cilagicin. These include antibiotic-resistant germs, such as vancomycin-resistant enterococci or methicillin-resistant staphylococci. According to the US Centers for Disease Control and Prevention, the resistant enterococci are considered a particularly serious threat because many patients in the hospital are infected with them.
The innovative antibiotic disturbs the construction of the cell walls of bacteria in two different ways. "Most likely, this new mechanism of action justifies the low development of resistance to Cilagicin," says Mast. However, the remedy can primarily harm gram -positive bacteria. Gram -negative pathogens have another protective layer that prevents many medication. But here too, Wang and his team have made progress. In January 2022, the researchers in the journal "Nature" reported on the discovery of the Macolacin antibiotic, which they had discovered using a similar method and the several gram -negative and multi -resistant germs.
"The strategy elegantly integrates methods of bioinformatics and synthetic biology," explains Mast. The molecular biologist Ryan Seipke from the University of Leeds in England wrote in an accompanying article on the study that the new discovery could "be the decisive factor in the fight against antimicrobial resistance". However, it still has to be shown how the resistance behavior in the clinical environment is.
Financing is also problematic: "On average, it takes 10 to 15 years and costs between 500 million and 1.1 billion euros for a newly discovered antibiotic to find its way into medical use," Mast reports. As more and more pharmaceutical companies withdraw from research into antibacterial agents, it is becoming increasingly difficult to find donors who finance clinical trials. Nevertheless, the microbiologist says: "Every newly found antibiotic active ingredient is an asset and helps to refill the currently idle antibiotic pipeline.«
