Bacteria modify their ribosomes to dodge antibiotics

Bacteria modify their ribosomes when exposed to widely used antibiotics, according to new research from the Centre for Genomic Regulation (CRG) in Barcelona. These subtle changes, which have been described in the journal Nature Communications, might be enough to alter the binding site of drug targets and constitute a possible new mechanism of antibiotic resistance.

Escherichia coli is a common bacterium which is often harmless but can cause serious infections. The researchers exposed E. coli to streptomycin and kasugamycin, two drugs which treat bacterial infections. Streptomycin has been a staple in treating tuberculosis and other infections since the 1940s, while kasugamycin is less known but crucial in agricultural settings to prevent bacterial diseases in crops.

Both antibiotics tamper with bacteria’s ability to make new proteins by specifically targeting their ribosomes. These molecular structures create proteins and are themselves made of proteins and ribosomal RNA. Ribosomal RNA is often modified with chemical tags that can alter the shape and function of the ribosome. Cells use these tags to fine-tune protein production.

The study found that, in response to the antibiotics, E. coli begins to assemble new ribosomes that are slightly different from the ones produced under normal conditions. Depending on which antibiotic was used, the new ribosomes lacked certain tags. The tags were specifically lost in the regions where antibiotics latch on to and halt protein production; the study found this made the bacteria more resistant to the drugs.

“We think the bacteria’s ribosomes might be altering its structure just enough to prevent an antibiotic from binding effectively,” said Anna Delgado-Tejedor, first author of the study and a PhD student at the CRG.

Bacteria are known to develop antibiotic resistance in different ways, including mutations in their DNA. Another common mechanism is their ability to actively pump and transport antibiotics out of the cell, reducing the concentration of the drug inside the cell to levels that are no longer harmful. The study demonstrates evidence of an entirely new survival strategy.

“E. coli is altering its molecular structures with remarkable precision and in real time; it’s a stealthy and subtle way of dodging drugs,” said Dr Eva Novoa, corresponding author of the study and a researcher at the CRG.

The researchers made the findings using advanced nanopore sequencing technology, which reads RNA molecules directly; previous techniques would process RNA molecules in such a way that it would remove the chemical modifications. As noted by Novoa, “Our approach has allowed us to see the modifications as they are, in their natural context.”

The study does not explore why or how the chemical modifications are lost in the first place. However, further research could explore the underlying biology of the adaptive mechanism and uncover new ways to combat one of the biggest looming crises in global health.

“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,” Novoa said.

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