Ribosomes are crucial to cells, because they translate messenger RNA molecules into the proteins that are necessary for cells to function. A new study has determined that bacteria can alter their ribosomes when they are exposed to antibiotics, which can change the structure of targets used by antibacterial drugs; this mechanism may be a newly discovered cause of antibiotic resistance. The findings have been reported in Nature Communications.
In this study, the researchers used the bacterium Escherichia coli, which is known as a resident of the human gastrointestinal tract. There are many forms of E. coli, however; some are harmless members of the human gut microbiome, other produce toxins and cause infection and disease, and scientists have modified some E. coli strains to use as workhorses in the laboratory.
In this work, various strains of E. coli were exposed to two antibacterial drugs: streptomycin and kasugamycin. Streptomycin has long been used to treat serious infections including tuberculosis. Kasugamycin is used in agriculture to reduce the threat bacterial diseases pose to crops. Both of these drugs disrupt a bacterial cell's ability to generate new proteins by taking aim at their ribosomes.
Ribosomes are complexes that consists of proteins and ribosomal RNA. Chemical tags can modify these ribosomal RNAs to affect ribosomal function, and carefully control protein production.
The investigators showed that when E. coli is exposed to these antibiotics, the bacterium starts to make ribosomes that are a little different from the cell's previous ribosomes that were made before antibiotic exposure. These new versions of ribosomes were found to lack certain chemical tags, depending on what antibiotic the cell was exposed to. The chemical tags were also removed from places where the drugs can bind and stop protein production, and the bacteria became more drug resistant.
“We think the bacteria's ribosomes might be altering its structure just enough to prevent an antibiotic from binding effectively,” said first study author and graduate student Anna Delgado-Tejedor of the Centre for Genomic Regulation (CRG).
Bacteria have many different ways to resist the effect of drugs, some of which involve genes or gene modifications. Others are related to efflux pumps that eliminate drugs from bacterial cells. Now, scientists have identified another potential resistance mechanism.
“E. coli is altering its molecular structures with remarkable precision and in real time. It’s a stealthy and subtle way of dodging drugs,” noted corresponding study author Dr. Eva Novoa, a researcher at the CRG.
The investigators don't yet know how the chemical modifications on ribosomes are removed, but the work continues.
“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 concluded.
Sources: Center for Genomic Regulation (CRG), Nature Communications