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New Insights into Combating Antibiotic-Resistant Bacteria

Recent projections predict a concerning rise in deaths from antibiotic-resistant infections, estimating that nearly 2 million people could perish annually by 2050. This sharp increase follows a report indicating that more than 1 million fatalities occurred each year from 1990 to 2021 due to these drug-resistant strains.

To combat this escalating public health challenge, researchers are exploring innovative strategies rooted in the complexities of bacterial infections. A significant study conducted by scientists at the University of California San Diego has unearthed a critical vulnerability in antibiotic-resistant bacteria.

Professor Gürol Süel, alongside partners from Arizona State University and Universitat Pompeu Fabra in Spain, delved into the antibiotic resistance mechanisms of the bacterium Bacillus subtilis. This inquiry was sparked by an intriguing question: why don’t antibiotic-resistant bacterial mutants dominate their populations despite their advantages? The expectation would be for these resistant strains to outcompete their non-resistant counterparts, yet that is not happening. What explains this paradox?

The findings, published in the journal Science Advances, reveal that antibiotic resistance comes at a significant physiological cost. While such resistance allows for survival under antibiotic pressure, it is also associated with limitations that impede broader dominance. According to the researchers, leveraging this cost could provide a pathway to curb the spread of antibiotic resistance.

“We’ve identified a critical weakness in antibiotic-resistant bacteria,” stated Süel, affiliated with UC San Diego’s Department of Molecular Biology. “This insight could allow us to suppress antibiotic resistance without relying on drugs or harmful substances.”

Spontaneous DNA mutations occur across all forms of life, including bacteria, with some mutations conferring antibiotic resistance. The research team concentrated on the ribosome’s physiological mechanisms—these cellular structures are essential for protein synthesis and genetic translation.

Cells universally depend on charged ions like magnesium for survival. Ribosomes particularly require magnesium to maintain their structural integrity. The recent study utilized atomic-scale modeling to show that mutant ribosomes, which confer antibiotic resistance, engage in an excessive competition for magnesium ions with adenosine triphosphate (ATP) molecules, which are vital energy sources for cells. The modeling indicated a competitive struggle between ribosomes and ATP for the limited magnesium availability within cells.

Through the examination of a ribosome variant known as “L22” within Bacillus subtilis, the research team discovered that this competition for magnesium significantly hampers the growth of L22 compared to the regular “wild type” ribosome. Consequently, the research indicates a physiological burden associated with the mutant strains that resist antibiotics.

“While antibiotic resistance is often viewed primarily as an advantage for bacteria, our findings highlight that managing magnesium limitations is crucial for their growth,” emphasized Süel.

This newly identified vulnerability could serve as a potential target for addressing antibiotic resistance without the need for pharmaceuticals or detrimental chemicals. Techniques such as chelating magnesium from bacterial environments could selectively suppress resistant strains while sparing beneficial wild-type bacteria. “Our research demonstrates that understanding the molecular and physiological traits of antibiotic-resistant bacteria can lead us to innovative non-drug-based control methods,” added Süel.

In a parallel effort, Süel and his team at the University of Chicago unveiled a bioelectronic device harnessing the natural electrical signals of specific skin bacteria to create alternative strategies for managing infections. This device has shown promise in mitigating the effects of Staphylococcus epidermidis, a bacterium commonly linked to hospital-acquired infections and antibiotic resistance. Both studies employed charged ions as a means to regulate bacterial behavior.

“As the effectiveness of existing antibiotics wanes, their widespread use has led to contamination across various ecosystems—from the Arctic to our oceans and groundwater,” remarked Süel. “Exploring drug-free alternatives for treating bacterial infections has become imperative, and our recent studies illustrate feasible pathways toward controlling antibiotic-resistant bacteria without pharmaceutical interventions.”

The research team included Eun Chae Moon, Tushar Modi, Dong-yeon Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan, and Gürol Süel.

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