Scientists have discovered two new mechanisms of action for established antibiotics, paving the way for the potential development of new antibiotic treatments.
A team based at the University of Exeter studied this bacterium. Coxiella barnet To investigate why they are so sensitive to doxycycline. Doxycycline, one of the most commonly prescribed antibiotics, is effective at low concentrations.
Cells build proteins with machines called ribosomes. Newly assembled proteins exit from here via exit channels. the team discovered that C. Burnety, Antibiotic molecules stack on top of each other to block ribosome exit channels, revealing a new mechanism by which doxycycline neutralizes bacteria. They hope this discovery could pave the way for a new generation of antibiotics derived from doxycycline.
Professor Nicholas Harmer, from the Institute of Life Systems at the University of Exeter, who led the study, said: “We used electron microscopy in this study, and recent advances now allow us to look at molecular structures in more detail than ever before. We were surprised by the number of important discoveries we made, including a completely new mechanism for how doxycycline works.” Coxiella. We now need to investigate whether this can be extended to other forms of bacteria that are resistant to antibiotics, which could open up very interesting avenues to new treatments. ”
The search for new antibiotics has become an international research priority to combat the crisis in which antibiotics become increasingly ineffective as bacterial resistance evolves, meaning that previously treatable infections can become deadly. Published in nature communications The research, funded by the UKRI Biotechnology and Biological Sciences Research Council and the Defense Science and Technology Research Institute, mainly investigated: Coxiella barnet. The bacteria is widespread in animals and can cause severe flu-like symptoms and death if inhaled by humans. People who work with livestock are especially at risk.
Using an electron microscope, the research team was able to observe ribosomes. Ribosomes decode genetic instructions carried by mRNA molecules and translate them into proteins, the workhorses of the cell. The researchers observed that doxycycline targets bacterial ribosomes by a previously known mechanism of action: blocking tRNA binding at the decoding center.
However, the researchers were surprised to discover that the second mechanism was effective. They observed a stack of three doxycycline molecules that completely blocked new proteins from leaving the ribosome, stopping protein production. This prevents the translation of the mRNA molecule, making the bacteria unable to grow and reproduce. A second additional mechanism was observed in more commonly studied bacteria E. coli. There, a single doxycycline molecule can fundamentally reconstitute ribosomes to a previously unseen inactive state.
This result really surprised us. I never expected to find such a beautiful mechanism explaining why antibiotics are so effective in treatment. C. Burnety infection. Interestingly, this may also apply to other bacteria, potentially providing new treatments for currently difficult-to-treat diseases. Our observation of reconstituted inactive ribosomes provides another potential route to highly potent future antibiotics. Our next step is to investigate whether these mechanisms can be harnessed to create new ways of antibiotics to fight infections, which are urgently needed around the world. ”
Dr William Stewart, University of Exeter Living Systems Institute Senior Author
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Reference magazines:
Stuart, W.S. Others. (2026). Cryo-EM reveals multiple mechanisms of ribosome inhibition by doxycycline. Nature Communications. DOI: 10.1038/s41467-026-73421-5. https://www.nature.com/articles/s41467-026-73421-5
