Super-antibiotic of the latest generation

The most effective antibiotic
Doctors have created fundamentally different antibiotics: they are 100 times more effective than the current ones

Larisa Aksenova, Newspaper.Roo

Having tested 663,000 different substances, scientists have created fundamentally different antibiotics. They turned out to be a hundred times more effective against tuberculous mycobacteria, they also affected the pathogens of anthrax and dysentery. Bacteria will not develop resistance to them soon.

The problem of resistance of microorganisms to antibiotics is one of the most acute in today's medicine. The causative agents of tuberculosis, anthrax and shigellosis (dysentery) may be defeated with the help of antibiotics with a fundamentally new mechanism of action. As a result of screening 663,000 promising candidate molecules, scientists from the University of Pennsylvania selected 46 that could selectively disrupt the process of bacterial protein synthesis at the key stage of "quality control" when reading ribosome information from RNA.

Ribosomes – factories for the production of protein – are found in all living organisms, both multicellular and unicellular – such as bacteria. It is here that the information recorded on the matrix RNA tape is materialized in the form of a protein. By reading every three nucleotides in the RNA sequence, the ribosome adds one amino acid to the protein synthesized in its bowels. The life of the owner of this most perfect intracellular system depends on the degree of accuracy of this process. To avoid mistakes, each stage of the multi–stage translation process in the cell is very tightly controlled, especially at the beginning, when RNA attaches to the ribosome, and at the end, when RNA must free up space on the ribosome for new matrices from which other proteins will be read. This complex control system is provided by a huge number of a wide variety of molecules.

But still, sometimes defects occur in the matrix RNA, which become apparent only at the terminal stage of protein synthesis. And at this stage, a protective mechanism called "trans-translation" is activated. Molecules-"nurses" of transport-matrix RNA (tmRNA) remove the protein product of the defective matrix from the ribosome, mark it for further destruction by proteases, and then help to remove and destroy the matrix itself.

The phenomenon of trans-translation was discovered by Kenneth Keiller, then a graduate student at Penn State University, in 1996. From that very moment, the scientist began to look for ways to influence the process of transtranslation in pathogenic bacteria. After all, if it were possible to interfere with the synthesis of bacterial proteins at the stage of "quality control", then this would eventually lead to a violation of the replication process – copying the genome of harmful microbes.

And now a group of researchers led by Keiler has achieved notable success in this search, the results of their work are published on June 3 in the journal Proceedings of the National Academy of Sciences (Ramadoss et al., Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity).

To find out which molecules can disrupt the process of trans-translation in bacteria, scientists tested 663,000 different substances. Screening was carried out in multi–moon Petri dishes, E. coli, a favorite model object for this kind of research, was used as an experimental microbe. As a result, 46 molecules from this huge list of substances were able to disrupt the trans-translation.

The next step was to test the effectiveness of 46 molecules on the translational apparatus of other pathogenic bacteria – representatives of the genus Shigella, genetically close to the genus Salmonella, causing acute intestinal disorders, shigellosis and dysentery, and Bacillus anthracis, the causative agent of anthrax.

One of the 46 molecules that disrupt the transtranslation process, it was assigned the classification number KKL-35, according to the authors of the study, turned out to be the most promising.

"We found that KKL-35 inhibits the growth of bacteria that are very distant in relation to relatives, and this suggests that this molecule may have antibiotic activity against a very wide range of microorganisms.

As for Shigella and Bacillus anthracis, we were able to show that in the presence of KKL-35, their cells died precisely because the molecule stopped the trans-translation process," says Kenneth Keiler, head of research.

Anthrax bacilli (Bacillus anthracis) killed with KKL-35.
The drug molecules fluoresce blue in ultraviolet light
(picture from the Pennsylvania State University press release
A new kind of antibiotic may be more effective against tuberculosis, anthrax – VM).

In addition to shigella and bacilli, scientists have also studied mycobacteria, namely Mycobacterium tuberculosis, which cause tuberculosis. The researchers found that compared to the currently used drugs, the KKL-35 molecule is 100 times more effective at suppressing the growth of these microbes.

As experts suggest, bacteria are unlikely to be able to quickly develop resistance to new antibiotics that will be developed on the basis of KKL-35, due to the specific target of their exposure. Of course, eventually resistant strains of bacteria will still arise, but this will not happen so quickly, and there will be a real chance to buy time from diseases.

Portal "Eternal youth" http://vechnayamolodost.ru04.06.2013