How Bacteria Outwit Antibiotics by Altering Ribosomal Structures
E. coli modifies ribosomes to evade antibiotics like streptomycin, revealing a novel resistance mechanism.
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Researchers have identified a new bacterial strategy for antibiotic resistance, centered on subtle changes to ribosomes. Published in Nature Communications, the study revealed that Escherichia coli modifies ribosomal structures when exposed to two widely used antibiotics, streptomycin and kasugamycin. This adaptation may hinder antibiotics from effectively binding to their targets.
Antibiotics and their ribosomal targets
Streptomycin, used to treat tuberculosis since the 1940s, and kasugamycin, crucial in agricultural disease prevention, both target bacterial ribosomes.
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Subscribe for FREERibosomes, responsible for protein synthesis, consist of proteins and ribosomal RNA (rRNA). Bacteria often chemically modify rRNA with tags that influence ribosomal structure and function, fine-tuning protein production.
Ribosome
A molecular machine in cells that synthesizes proteins by translating messenger RNA (mRNA). Ribosomes are essential for cell survival and are often targeted by antibiotics.Ribosomal RNA (rRNA)
A type of RNA that forms the structural and functional core of ribosomes. It can undergo chemical modifications that impact its interaction with antibiotics.The study demonstrated that when exposed to antibiotics, E. coli produces ribosomes lacking specific chemical tags. These tags are normally located in the regions targeted by the antibiotics. Their absence alters the ribosome's structure, reducing the drugs' effectiveness.
A novel resistance mechanism
While bacterial resistance is typically associated with DNA mutations or the expulsion of antibiotics from cells, the researchers suggest this represents a new approach. E. coli adapts its ribosomes in real-time, enabling a subtle but effective evasion of antibiotic action.
“We think the bacteria's ribosomes might be altering its structure just enough to prevent an antibiotic from binding effectively.”
Anna Delgado-Tejedor
Cutting-edge methods to reveal ribosomal changes
The findings were made possible by nanopore sequencing technology, which enables the direct analysis of RNA molecules, preserving their chemical modifications. Traditional methods often strip these modifications, obscuring critical insights.
Nanopore sequencing
A technology used to sequence DNA or RNA molecules by passing them through a tiny pore, allowing the analysis of chemical modifications without altering the molecules.Questions for future research
This study highlights the dynamic ability of bacteria to adapt molecular structures in response to threats. However, the mechanism behind the loss of ribosomal chemical modifications remains unclear. Understanding this process could lead to new therapeutic strategies aimed at combating antibiotic resistance, a major global health challenge that has caused millions of deaths since 1990.
Reference: Delgado-Tejedor A, Medina R, Begik O, et al. Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites. Nat Comm. 2024;15(1):10054. doi: 10.1038/s41467-024-54368-x
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