Bacteria change their ribosomes to avoid antibiotics

Escherichia coli is a common bacterium that is often harmless but can cause serious infections. The research team exposed E. coli bacteria to streptomycin and kasugamycin, two drugs that treat bacterial infections. Streptomycin has been a mainstay of treatment for tuberculosis and other infections since the 1940s, while kasugamycin is less well known but is critical in agriculture for preventing bacterial diseases in crops.

Both antibiotics change the ability of bacteria to make new proteins by specifically targeting their ribosomes. These molecular structures create proteins and are made up of proteins and ribosomal RNA. Ribosomal RNA often has chemical modifications that can change the shape and function of the ribosome. Cells use these modifications to regulate protein production.

The study found that in response to antibiotics, E. coli begins to assemble new ribosomes, slightly different from those produced under normal conditions. Depending on the antibiotic used, the new ribosomes do not have certain modifications. These modifications are especially lost in regions where antibiotics bind and stop protein production. The study found that this makes bacteria more resistant to drugs.

Modifying ribosomes to prevent antibiotic effect

“We believe that bacterial ribosomes may be structurally altered enough to prevent efficient binding of antibiotics,” says Anna Delgado Tejedor, first author of the study and a graduate student at the Center for Genomic Regulation (CRG) in Barcelona.

Bacteria are known to develop resistance to antibiotics in a variety of ways, including mutations in their DNA. Another common mechanism is its ability to actively pump and transport antibiotics out of the cell, reducing the concentration of the drug inside to a level that is no longer dangerous.

The study tests an entirely new coping strategy. “I. coli changes its molecular structure with amazing precision and in real time. It is a hidden and subtle way to avoid drug use,” says Dr. Eva Novoa, lead author of the study, ICREA Research Professor and CRG Fellow.

A new way to fight the health crisis

The results were made using advanced nanopore sequencing technology, which directly reads RNA molecules. Previous methods processed RNA molecules in a way that eliminated chemical modifications. “Our approach allowed us to see the changes for what they were, in their natural context,” says Dr. Novoa.

The study does not address why or how the chemical modifications are lost. Future research could delve deeper into the underlying biology of this adaptive mechanism and reveal new ways to combat one of the biggest looming crises in global health. Global antimicrobial resistance has claimed at least one million lives every year since 1990 and is projected to cause an additional 39 million deaths between now and 2050.

“If we can dig deeper and understand why these modifications are lost, we may be able to develop new strategies that prevent bacteria from losing them, or develop new drugs that bind to altered ribosomes more effectively,” Dr. Novoa concludes.

Fountain: CRG