Researchers from Skoltech and other scientific centres have presented an updated reporter system – a tool for discovering new antibiotics. The system enables screening of compounds that disrupt RNA synthesis in Gram‑negative bacteria – including multidrug‑resistant Pseudomonas aeruginosa, a dangerous hospital pathogen that has already adapted to existing antibiotics. Targeting RNA synthesis is considered a promising mechanism of action for new drugs, as few such agents are currently available and bacteria have not yet developed widespread resistance to them. The study was published in the International Journal of Molecular Sciences.
Uncontrolled antibiotic use drives the development of drug resistance in bacteria, making previously harmless microbes dangerous. Pseudomonas aeruginosa, for example – common in water and soil and prone to colonising medical equipment – has over the past 50 years acquired resistance to several antibiotic classes, becoming a major hospital pathogen. Staphylococcus aureus, which lives on healthy human skin, can cause pneumonia and other infections when immunity is weakened; it too has adapted to multiple antibiotics that once killed it.
“One of the main ways to combat antibiotic resistance is to discover new active substances. A crucial step in studying new compounds is identifying their molecular mechanism of action, which can later help overcome bacterial resistance,” said the study’s principal investigator, Dmitry Lukyanov, a senior lecturer at Skoltech’s Centre for Bio‑ and Medical Technologies.
Knowing the mechanism of action of each drug is essential for detailed study and for chemical modification, Lukyanov noted.
“If a bacterium has developed resistance to one compound, that does not mean all similar molecules should be abandoned. Sometimes a compound can be slightly modified and become effective again,” he added.
The Skoltech team has refined a targeted screening tool for antibiotics against Gram‑negative bacteria such as Pseudomonas aeruginosa, making it sensitive to compounds that disrupt RNA biosynthesis – a key process for bacterial cell survival. This mechanism is promising because pathogens have not yet had time to adapt to it, and relatively few such drugs are on the market – mainly rifampicin and fidaxomicin.
