According to a study published in Nature Communications today bacteria modify their ribosomes after being exposed to commonly used antibiotics. These subtle modifications could be sufficient to change the drug binding sites and create a new method of resistance. Escherichia Coli can be a harmless bacterium that causes serious infections.
Researchers exposed E. coli bacteria to two antibiotics that treat bacterial infection, streptomycin & kasugamycin. Streptomycin, a drug used to treat tuberculosis since 1940s and many other infections, is now less common but still vital in agriculture for preventing bacterial disease in crops. Both antibiotics interfere with the ability of bacteria to produce new proteins, by targeting their ribosomes. They are molecular structure that creates proteins. These structures themselves are made up of ribosomal DNA and proteins. Ribosomal DNA is sometimes modified by chemical tags which can change the function and shape of the ribosome. These tags are used by cells to optimize protein production.
According to this study, E. coli starts to assemble ribosomes slightly different than those produced in normal conditions when it is exposed to antibiotics. The new ribosomes differed depending on the antibiotics used. Tags were lost specifically in regions that antibiotics attach to, halting protein production. This made bacteria resistant to drugs, according to the study. Anna Delgado Tejedor is the first author and PhD student of the study at the Centre for Genomic Regulation in Barcelona.
It is known that bacteria can develop resistance to antibiotics through mutations of their DNA. One common mechanism involves their ability to pump and transport the antibiotics outside the cell. This reduces the amount of drug in the cell until it is no longer harmful. The study provides evidence for a new strategy of survival. “19459003” says Dr. Eva Novoa. She is the corresponding author and a researcher with the CRG.
Researchers made their findings using nanopore technology that reads RNA directly. RNA molecules were processed in the past to remove chemical modifications. “Our approach has allowed us to see the modifications as they are, in their natural context,” says Dr. Novoa. The study did not investigate why and how chemical modifications were lost. Research could be conducted to explore the biology behind the adaptive mechanism, and find new approaches for combating one of the most pressing global health crises. Since 1990, global antimicrobial resistant has caused at least 1 million deaths per year. It is predicted that this number will rise to 39 millions by 2050.
“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,” says Dr. Novoa.
