2024-02-15 20:00:00
It’s a game of cat and mouse: Once an antibiotic effectively prevents bacteria from multiplying, only those that happen to carry genes that can render the antibiotic harmless survive. These mutant bacteria multiply and at some point there will only be resistant microbes against which doctors are powerless. But now a research team at Harvard University believes they have discovered a method for developing antibiotics that can win the race against evolution.
When the antibiotic penicillin was used for the first time in 1941 to treat infections with disease-causing bacteria, it was a milestone in medical history. Penicillin and many other antibiotics have now become a blunt sword in many places.
The new antibiotic cresomycin, how it blocks the ribosome and thus the protein production of the bacterium Thermus thermophilus.
© YURY POLIKANOV/UNIVERSITY OF ILLINOIS CHICAGO
The number of bacterial strains that are resistant to one, several or even all available antibiotics is constantly increasing – with fatal consequences: In 2019 alone, 1.27 million people worldwide died from bacterial infections that could no longer be treated due to such resistance. Now the research team led by Andrew Myers from Harvard University in Cambridge has artificially produced a new antibiotic: cresomycin. The trade magazine “ScienceHowever, this new synthesis is not presented solely because of this one active ingredient.
Resistant to resistance
Rather, it is the method by which the substance was developed that deserves this attention. “It shows a path to antibiotics that can also deal with multi-resistant germs,” says Mark Brönstrup, chemist at the Helmholtz Center for Infection Research in Braunschweig. He was not involved in the Harvard study.
A good sign for the future discovery of antibacterial agents.
Andrew MyersHarvard University, Cambridge, USA
Many classic antibiotics, such as lincomycin, block the production of proteins by disabling the ribosomes, the protein factories in the bacteria. This is also practical because the ribosomes of bacteria are fundamentally different from those in humans, animals and plants, so no side effects are to be expected.
But so far, bacteria have always found ways to change the structure of their ribosomes so that lincomycin or other antibiotics no longer “fit”. Antibiotics can be modified and adapted to such changes in the shape of the ribosomes, such as clindamycin. “However, the conventional chemical modifications of these substances reach their natural limits and find it difficult to overcome the resulting resistance,” says Mark Brönstrup.
Threatening age of deaths from infections Where there are problems with the development of new antibiotics
Andrew Myers and his group therefore first examined the places on the ribosome to which the antibiotic molecules attach. They then used the computer to calculate a molecule that fits this binding site as closely as possible and then produced it fully synthetically. “That was definitely a big hurdle because for a long time such completely synthetic processes were considered far too complex to be realized,” says Brönstrup. But this is important because semi-synthetic processes such as the biotechnical production of drugs are usually more complex and expensive and are therefore not suitable for antibiotics, which have to be as cheap as possible.
Stiff antibiotics work better
In addition to the good fit, the cresomycin molecule is also unusually stiff. Antibiotics are normally relatively mobile and nestle into the binding trough at the ribosome. This flexibility of the molecule also means that it comes apart more easily. In fact, many microbes become resistant because the shape of the binding well in the ribosome is changed by random mutations, so that antibiotic molecules can hardly or not survive.
The stiff cresomycin remains in place once bound. The ribosome remains blocked. “This stiffening strategy is very interesting and could also be used for other active ingredients,” says Brönstrup. And the concept could be relevant to combating many pathogenic bacteria.
More on the subject:
Multi-resistant germs Researchers discover new antibiotic Future of antibiotics? A new type of substance could kill bacteria precisely. Creeping pandemic where resistant germs emerge
Cresomycin, for example, not only inhibits different types of bacteria, but above all multi-resistant strains Staphylococcus aureus (known as “MRSA”), Escherichia coli and Pseudomonas aeruginosa. At least that’s what experiments with cell cultures and infected mice showed. Clinical tests on patients are still pending. Nevertheless, Myers’ team is optimistic: “We think our results bode well for the future discovery of antibacterial agents that are broadly effective against antibiotic resistance.” (my skb)
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