A new study from the Centre for Genomic Regulation (CRG) in Barcelona reveals that bacteria can modify their ribosomes when exposed to commonly used antibiotics, potentially contributing to antibiotic resistance. These subtle changes could alter the drug-binding sites on ribosomes, making antibiotics less effective.
The study focused on *Escherichia coli* (E. coli), a bacterium that is typically harmless but can cause serious infections. The researchers exposed E. coli to two antibiotics, streptomycin and kasugamycin.
Streptomycin has been widely used since the 1940s to treat tuberculosis and other infections. At the same time, kasugamycin, though less well-known, plays a key role in agriculture in preventing bacterial diseases in crops.
The study found that streptomycin and kasugamycin interfere with bacteria’s ability to produce proteins by targeting their ribosomes, which are made of proteins and ribosomal RNA (rRNA). rRNA is often chemically modified with tags that help regulate the ribosome’s shape and function, optimizing protein production.
When *E. coli* was exposed to these antibiotics, it started producing new ribosomes that differed slightly from the normal ones. These new ribosomes lacked specific chemical tags, especially in the areas where the antibiotics typically bind to stop protein production. This alteration in the ribosomes made the bacteria more resistant to the antibiotics.
Anna Delgado-Tejedor, the study’s first author and PhD student at the Centre for Genomic Regulation (CRG) in Barcelona, said, “We think the bacteria’s ribosomes might be altering their structure just enough to prevent an antibiotic from binding effectively.”
Bacteria typically develop antibiotic resistance through mechanisms like DNA mutations or pumping antibiotics out of the cell to reduce their effectiveness. However, the study presents a novel survival strategy in E. coli, where the bacteria alter their ribosomal structures with remarkable precision to evade antibiotics.
Dr. Eva Novoa, the study’s corresponding author, described this as a subtle and stealthy way of avoiding the drugs.
The researchers used advanced nanopore sequencing technology to directly read RNA molecules, allowing them to observe chemical modifications in the ribosomes as they occur in their natural state. This new approach contrasts with previous techniques to remove these modifications, providing deeper insights into how *E. coli* adapts to antibiotic pressure in real-time.
The study does not investigate the reasons or mechanisms behind the loss of chemical modifications in the ribosomes, leaving this as an area for future research. Understanding the underlying biology of this adaptive process could provide new insights into combating antibiotic resistance, a major global health threat.
Since 1990, antimicrobial resistance has been responsible for at least one million deaths annually, and it is predicted to cause an additional 39 million deaths between now and 2050.
Dr. Novoa said, “If we can delve deeper and understand why they are shedding these modifications, we can create new strategies that prevent bacteria from shedding them in the first place or make new drugs that more effectively bind to the altered ribosomes.”
Journal Reference:
- Delgado-Tejedor, A., Medina, R., Begik, O. et al. Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites. Nat Commun 15, 10054 (2024). DOI: 10.1038/s41467-024-54368-x