Bacteria are known to develop resistance to antibiotics through various mechanisms, but recent research has uncovered an intriguing new way in which bacteria might adapt to the presence of these drugs. According to a study published in Nature Communications, bacteria modify their ribosomes when exposed to antibiotics, a subtle but potentially significant alteration that could provide a new avenue for antibiotic resistance.
The research team, led by Anna Delgado-Tejedor at the Center for Genomic Regulation in Barcelona, focused on Escherichia coli (E. coli), a bacterium that is commonly found in the human gut but can also cause serious infections, such as urinary tract infections, pneumonia, and sepsis. In the study, the researchers exposed E. coli to two different antibiotics: streptomycin and kasugamycin. Streptomycin has been a cornerstone in treating tuberculosis and various other bacterial infections since its discovery in the 1940s, while kasugamycin, although less well-known, is crucial in agriculture to prevent bacterial diseases in crops.
Both of these antibiotics work by targeting the bacterial ribosome, a molecular machine responsible for protein synthesis. Ribosomes are composed of ribosomal RNA (rRNA) and proteins, and the rRNA is often chemically modified to help regulate protein production. The antibiotics target specific sites on the ribosome, blocking protein synthesis and ultimately killing the bacteria.
However, the researchers discovered that E. coli, when exposed to streptomycin or kasugamycin, began to produce new ribosomes with altered structures. These modified ribosomes were missing certain chemical tags—modifications to the rRNA—specifically in the regions where the antibiotics bind to inhibit protein production. The loss of these chemical tags allowed the ribosomes to continue functioning, making the bacteria more resistant to the antibiotics.
This finding suggests a novel mechanism of antibiotic resistance. Instead of the more commonly known mechanisms, such as genetic mutations or the active pumping of drugs out of the bacterial cell, E. coli appeared to be adapting to the presence of antibiotics by subtly altering its ribosomal structure in real time. The bacteria seemed to be “dodging” the antibiotics by modifying the very molecules that the drugs target.
“We think the bacteria’s ribosomes might be altering their structure just enough to prevent an antibiotic from binding effectively,” said Anna Delgado-Tejedor, the first author of the study. This molecular modification occurs at the level of the ribosome’s rRNA, which is usually modified with chemical tags. These tags help fine-tune the protein synthesis process, and in the case of antibiotic exposure, the bacteria seem to shed some of these modifications in the regions where the drugs bind.
The research team utilized advanced nanopore sequencing technology to observe these modifications. This method allowed the scientists to directly read RNA molecules without removing their chemical modifications, offering a more accurate picture of how the ribosomes changed in response to antibiotics. Previous technologies would often strip away these chemical modifications during analysis, masking important details about how the bacteria adapted.
“This approach has allowed us to see the modifications as they are, in their natural context,” explained Dr. Eva Novoa, the corresponding author of the study. “E. coli is altering its molecular structures with remarkable precision and in real time. It’s a stealthy and subtle way of dodging drugs.”
While the study provides important insights into this new mechanism of antibiotic resistance, it does not yet explain how or why the bacteria shed these chemical modifications in the first place. This opens the door for further research to explore the underlying biological processes involved. Understanding the causes and mechanisms behind these changes could lead to the development of new strategies to combat antibiotic resistance.
Antimicrobial resistance (AMR) is a growing global health crisis. It is estimated that AMR causes at least one million deaths per year, and it is predicted that the number could rise to 39 million by 2050 if current trends continue. Researchers like Dr. Novoa believe that by better understanding how bacteria adapt to antibiotics, it may be possible to develop more effective drugs or create strategies to prevent bacteria from shedding these crucial chemical modifications.
“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,” said Dr. Novoa.
This study highlights the complexity of bacterial resistance mechanisms and emphasizes the need for ongoing research to stay ahead of evolving pathogens. The discovery of this novel strategy for antibiotic resistance could be a crucial step in addressing one of the most pressing health challenges of the 21st century.
Source: Center for Genomic Regulation