New research from Barcelona’s Centre for Genomic Regulation indicates that bacteria may modify their ribosomes in response to common antibiotics. This could contribute to the development of antibiotic resistance. The subtle changes may alter drug binding sites in ribosomes and make antibiotics less efficient.
This study was focused on E. coli, a bacterium which is usually harmless but has the potential to cause severe infections. Researchers exposed E. coli bacteria to streptomycin, and kasugamycin.
Since the 1940s, streptomycin is widely used to treat infections such as tuberculosis. Kasugamycin is a less-known antibiotic that plays a crucial role in agriculture to prevent bacterial disease in crops.
Researchers found that streptomycin (and kasugamycin) interfered with the ability of bacteria to produce protein by targeting ribosomes. Ribosomes are composed of proteins and ribosomal RNA. The rRNA can be chemically altered with tags to help optimize protein production.
After *E.coli* exposed these antibiotics to the ribosomes it produced, they were slightly different from normal ones. The new ribosomes were missing specific chemical tags in areas that antibiotics usually bind, to prevent protein production. The bacteria became more resistant to antibiotics after this alteration.
Anna Delgado Tejedor is a PhD student and first author of the study at the Centre for Genomic Regulation in Barcelona. We think that the bacteria’s structure might have been altered just enough by ribosomes to stop an antibiotic from binding.
Bacteria develop resistance to antibiotics through mechanisms such as DNA mutations and pumping out antibiotics from the cell. The study reveals a new survival strategy for E. coli where bacteria change their ribosomal structure with incredible precision in order to evade anti-biotics.
The study’s co-author, Dr. Eva Novoa described it as a sneaky and subtle way to avoid the drugs.
Researchers used nanopore technology to read directly RNA molecules. This allowed them to see chemical modifications occurring in the ribosomes in their original state. The new method contrasts previous methods to remove the modifications and provides deeper insight into how E. coli adapts in real time to antibiotic pressure.
This study did not examine the mechanisms or reasons behind the reduction of chemical modification in ribosomes. Future research will be needed to investigate this area. The underlying biology behind this adaptive process may provide valuable insights in combating the global threat of antibiotic resistance.
Antimicrobial resistance is responsible for at minimum one million deaths per year since 1990. It’s predicted that it will cause 39 millions more deaths by 2050.
Dr. Novoa said, If we could understand the reasons why bacteria shed these modified ribosomes, then we might be able to create strategies to prevent them from being shed in the first instance or develop new drugs which more efficiently bind the altered ribosomes.
Journal Reference
- Delgado-Tejedor, A., Medina, R., Begik, O. et al. Native RNA Nanopore Sequencing reveals antibiotic-induced losses of rRNA modification in A-and P-sites. Nat Commun 15, 10054 (2024). DOI: 10.1038/s41467-024-54368-x
