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SAN DIEGO — In the ongoing battle against antibiotic-resistant “superbugs,” researchers have uncovered an unexpected vulnerability that could change how we fight these deadly infections – and it all comes down to a microscopic competition for resources.
The discovery comes at a crucial time. Current estimates paint a grim picture: drug-resistant infections already claim over one million lives annually, with deaths projected to nearly double to two million per year by 2050.
However, a team led by researchers at the University of California-San Diego may have found a new way to tackle this crisis without relying on traditional antibiotics. Their research, published in Science Advances, reveals that antibiotic-resistant bacteria have an inherent weakness – one that might explain why these seemingly unstoppable superbugs haven’t completely taken over.
“We discovered an Achilles heel of antibiotic resistant bacteria,” says Professor Gürol Süel from UC San Diego’s Department of Molecular Biology in a media release. “We can take advantage of this cost to suppress the establishment of antibiotic resistance without drugs or harmful chemicals.”
The team studied a common bacterium called Bacillus subtilis, focusing on why antibiotic-resistant strains don’t always dominate their non-resistant counterparts. What they found was surprising. The very mutations that make bacteria resistant to antibiotics also create an unexpected weakness.
Think of it as a tug-of-war inside the bacterial cell. The researchers discovered that in resistant bacteria, essential cellular components called ribosomes (which help make proteins) become unusually greedy for magnesium, a vital mineral. This creates internal competition with ATP molecules – essentially the cell’s energy currency – which also need magnesium to function. It’s like having two vital workers fighting over limited resources, ultimately making the resistant bacteria less efficient at growing and spreading.
This finding is particularly exciting because it suggests a new way to fight resistant bacteria without using traditional antibiotics. Scientists might be able to target this weakness by manipulating magnesium levels in bacterial environments, potentially stopping resistant strains while leaving beneficial bacteria unharmed.
The discovery is part of a broader push to find drug-free alternatives to fighting bacterial infections. In a separate study last October, Süel and his colleagues also developed a bioelectronic device that uses bacterial electrical activity to combat infections, successfully reducing the harmful effects of a common hospital-acquired infection.
“We are running out of effective antibiotics and their rampant use over the decades has resulted in antibiotics being spread across the globe, from the arctic to the oceans and our groundwater,” Süel notes. “Drug-free alternatives to treating bacterial infections are needed and our two most recent studies show how we can indeed achieve drug-free control over antibiotic resistant bacteria.”
This breakthrough offers hope in what has become one of modern medicine’s most pressing challenges. By understanding and exploiting these natural vulnerabilities, researchers may have found a new way to turn the tide in the fight against antibiotic resistance – without adding more antibiotics to our already oversaturated environment.
Paper Summary
Methodology
The researchers investigated a specific ribosome variant in Bacillus subtilis bacteria that offers resistance to certain antibiotics but might come at a physiological cost. They focused on the role of magnesium ions (Mg²⁺), essential for ribosome stability and cellular energy storage. The team used a mix of lab experiments, computational modeling, and bioluminescence assays. Bacterial strains with and without the ribosome mutation were grown under different magnesium levels and exposed to antibiotics to see how they performed. They also measured magnesium and ATP (cellular energy) levels to uncover how the mutation impacts bacterial physiology.
Key Results
The study showed that bacteria with the antibiotic-resistant ribosome mutation (L22*) had a harder time surviving when magnesium was scarce. Although the mutation helped bacteria resist antibiotics, it caused them to soak up too much magnesium, leaving less for other vital processes like producing energy (ATP). This made the mutated bacteria weaker in low-magnesium environments compared to normal bacteria. However, when magnesium levels were high, the mutated bacteria thrived under antibiotic pressure.
Study Limitations
The experiments were conducted in controlled lab conditions, which might not perfectly mimic real-world environments. The study focused on a single ribosome mutation in one bacterial species, so the findings might not apply universally. The computational models used make assumptions that may not fully capture all biological complexities.
Discussion & Takeaways
This research highlights a trade-off: the ribosome mutation provides antibiotic resistance but makes bacteria more dependent on magnesium. This creates a potential vulnerability — targeting magnesium availability might help control antibiotic-resistant bacteria. The study also sheds light on the broader role of magnesium in linking ribosome function and energy production, suggesting new strategies to combat resistance by exploiting these biological connections.
Funding & Disclosures
This study was supported by a diverse range of funding sources, reflecting its interdisciplinary and international nature. The National Institute of General Medical Sciences provided grant R35 GM139645 to support foundational research efforts by Gürol Süel. The Army Research Office funded critical components of the work under grants W911NF-22-1-0107 and W911NF-1-0361 (G.M.S.), while additional funding was provided by the Bill & Melinda Gates Foundation (INV-067331, G.M.S.).
Contributions from study author Jordi Garcia-Ojalvo were supported by the Spanish Ministry of Science, Innovation and Universities and FEDER projects PID2021-127311NB-I00 and CEX2018-000792-M, as well as the Generalitat de Catalunya’s ICREA Academia program. Researcher S. Banu Ozkan received support from the National Science Foundation Division of Molecular and Cellular Biosciences (award 1715591) and the Gordon and Betty Moore Foundation. The authors have declared no competing interests, ensuring the integrity and impartiality of the research.
