Russian scientists have unraveled the mechanism of action of a potent antibiotic, a mystery for over half a century, which could now aid in the fight against modern superbugs, reports the newspaper Izvestia.
The mechanism of the antibiotic bottromycin A2 was detailed by specialists from Skoltech in collaboration with researchers from the Kurchatov Institute. The compound, first isolated in Germany in 1957, can kill pathogens against which other drugs are powerless. However, in its original form, the molecule was unstable in blood, preventing its development into a viable drug.
“We conducted numerous experiments and determined the precise mechanism of action of bottromycin A2, and it turned out to be different from all previously proposed versions. Moreover, this mechanism is completely new and even unique compared to the mechanisms of known antibiotics, which partly explains the long time it took to discover it,” said Skoltech PhD student Inna Volynkina.
It turns out that bottromycin kills bacteria by blocking not protein assembly itself, but the delivery of one of its building blocks—glycine. This prevents the delivery of protein-building materials to the assembly machinery, thereby disrupting the vital processes of the pathogenic bacterial cell.
“Bottromycin A2 has a unique mechanism for inhibiting protein synthesis: it selectively blocks translation specifically when glycine incorporation is required. This discovery not only expands fundamental understanding of antibiotic interactions with bacterial cells but also opens new prospects for developing antimicrobial agents with a targeted mechanism of action,” said Elena Polesskova, a senior researcher at the Molecular and Radiation Biophysics Department of the Kurchatov Institute Research Center.
The uniqueness of bottromycin’s mechanism of action makes the emergence of cross-resistance to other antibiotics unlikely, making the compound promising for the development of next-generation drugs. Additionally, it is possible that other molecules operating via similar mechanisms exist in nature, opening new horizons for researchers.