The new molecule blocks a site on the bacterial ribosome that is not currently a target for clinical antibiotics.
Antibiotic resistance is one of the most difficult problems in modern medicine. As bacteria are repeatedly exposed to existing drugs, they develop defense mechanisms that weaken their effectiveness. Therefore, the discovery of a new mechanism of action is particularly important: not just another molecule, but a different way to damage the bacterial cell.
Researchers at McMaster University in Canada report a new antibiotic candidate called menicomycin. According to the university and the article published in Nature, the molecule acts on a site on the bacterial ribosome that has not been exploited as a target for clinical antibiotics. The ribosome is the cellular machinery that makes proteins, and without proper protein production, the bacteria cannot survive. (McMaster News)
No more hitting the same targets
Many antibiotics act on a relatively limited number of targets in the bacterial cell. Some damage the cell wall, others disrupt DNA replication or protein production. Even within the ribosome, different drugs tend to target familiar areas. The problem is that bacteria that have repeatedly encountered such stress can develop resistance mechanisms, and sometimes cross-resistance to similar drugs.
Meniomycin is different in that it binds to the E site on the large subunit of the bacterial ribosome. According to Nature, it prevents the tRNA end from properly entering this site, thereby disrupting the translocation step—the precise movement that allows the ribosome to move along the mRNA and continue building the protein. (Nature)
In simpler terms, you can think of the ribosome as an assembly line. At each step, a component enters, joins the chain, and then has to exit at the correct place to make room for the next step. Meningomycin blocks the “exit path.” When the exit is blocked, the assembly line stalls.
Old bacterium, new molecule
The origin of menicomycin is as interesting as its mechanism. It was discovered in the soil bacterium Streptomyces rimosus, which has been known since the 1950s as the source of oxytetracycline, one of the important antibiotics discovered during the golden age of drug discovery in soil bacteria. Precisely because S. rimosus had been studied for decades, it was commonly thought that it had already been “exhausted” as a source of new drugs.
The researchers came back to it with a different approach. Instead of settling for the prominent and common compounds in the mixture, they used advanced separation methods to filter out oxytetracycline and other abundant substances, thus reaching rarer molecules that had previously been lost in the chemical noise of the mixture.
The implications are broader than the molecule itself. It is possible that some of the sources abandoned in the search for new antibiotics are not truly empty, but simply untested with the right tools. If so, a smart return to “old” bacteria could reopen chemical reservoirs that were thought to be closed.
Against resistant bacteria, but still at an early stage
According to McMaster, meningomycin has shown early efficacy against important pathogens, including Salmonella, E. coli and Klebsiella. The Nature article notes that it is able to kill multidrug-resistant Enterobacteriaceae and is not susceptible to resistance mechanisms associated with existing clinical antibiotics.
However, it is important to phrase the finding with caution. Menimycin is not an over-the-counter drug, and it is not an approved treatment for patients. It is an antibiotic candidate in early development. The research team has already shown, according to McMaster, that the molecule is not toxic to human cells in initial experiments and works in a controlled laboratory model of infection. The researchers are now trying to improve its duration of activity in the body, and have already created 60 derivatives of the molecule to select the best candidate for further development.
A new goal in an old struggle
The importance of meningomycin is not just that it could become a drug in the future, but that it points to a new target. If the E site on the bacterial ribosome can indeed be a weak point, it may be possible to develop a broader family of antibiotics around it. This is especially important at a time when the rate of resistance emergence is rapid, while the rate of approval of new drugs is slow.
As in many cases of drug discovery, there is a long way to go. Additional tests are needed for safety, efficacy, range of activity, stability in the body, dosage, and side effects. But the mere identification of a new mode of action is a significant research achievement: It adds another possible direction for combating bacteria that have already learned to defend themselves against many of the existing drugs.
Short FAQ:
Is meningomycin available as a medicine? No. This is an antibiotic candidate in early stages of development.
What's new in its mechanism? It targets the E site on the bacterial ribosome, a target that is not exploited by existing clinical antibiotics.
What bacteria was it tested against? According to the researchers, it showed early activity against important bacteria including Salmonella, E. coli, and Klebsiella.
More on the subject on the Haaretz website
