To address the alarming rise in antibiotic resistance, scientists are exploring how bacterial infections operate. A recent study has identified a weakness related to magnesium levels, which could be leveraged to combat the spread of antibiotic resistance.
Current projections suggest that the number of fatal antibiotic-resistant infections will increase significantly within the next 25 years. A recent study indicated that over 1 million people died annually from drug-resistant infections between 1990 and 2021, with forecasts anticipating almost 2 million deaths each year by 2050.
In response to this urgent public health issue, researchers are investigating new strategies by delving into the complex processes behind bacterial infection. A study spearheaded by scientists at the University of California, San Diego, has uncovered a weakness in antibiotic-resistant bacterial strains.
Collaborating with teams from Arizona State University and Universitat Pompeu Fabra in Spain, Professor Gürol Süel and his colleagues at UC San Diego’s School of Biological Sciences examined the antibiotic resistance of the bacterium Bacillus subtilis. They sought to understand why mutant bacteria, which gain a survival advantage through antibiotic resistance, do not dominate their population. Intuitively, such bacteria should thrive over their non-resistant counterparts, yet they do not. Why is that?
The findings, published in the journal Science Advances, reveal that antibiotic resistance carries a hidden cost. While it confers certain survival benefits, the researchers discovered a physiological limitation that prevents these mutant strains from flourishing. This insight could potentially be harnessed to halt the proliferation of antibiotic resistance.
“We’ve found a vulnerability in antibiotic-resistant bacteria,” stated Süel, a member of the Department of Molecular Biology at UC San Diego. “This disadvantage can be exploited to inhibit the spread of antibiotic resistance without the need for drugs or harmful substances.”
All living cells, including bacteria, experience random DNA mutations, some of which can lead to antibiotic resistance. The research team focused on the physiological roles of ribosomes, the cellular machinery essential for protein synthesis and the translation of genetic information.
Cells depend on charged ions, like magnesium, for survival. Ribosomes, in particular, rely on magnesium ions to maintain their structure and function. However, the latest research utilized atomic-scale modeling, revealing that mutant ribosome variants that confer antibiotic resistance compete intensely for magnesium ions against adenosine triphosphate (ATP) molecules, which are critical for cellular energy. This dynamic creates a competitive struggle within the cell for magnesium availability.
By examining a ribosome variant named “L22” in Bacillus subtilis, the team discovered that the competition for magnesium limits the growth of L22 more than that of a typical, non-resistant “wild type” ribosome. This competition results in a significant physiological burden for the mutant bacteria.
“While antibiotic resistance is often seen as a major advantage for bacteria, we’ve found that managing magnesium scarcity is more crucial for their growth,” explained Süel.
This newly identified vulnerability can serve as a target for mitigating antibiotic resistance without relying on drugs or toxic chemicals. For instance, it might be feasible to remove magnesium ions from the bacterial environment, selectively hindering resistant strains while sparing beneficial wild type bacteria. “Our research indicates that by better understanding the molecular and physiological traits of antibiotic-resistant bacteria, we can discover new, drug-free methods to control them,” Süel said.
In October, Süel and his colleagues from the University of Chicago revealed another innovative approach to address the challenge posed by antibiotic-resistant bacteria. They developed a bioelectronic device that utilizes the natural electrical activity of specific bacteria present on human skin, opening another avenue for drug-free infection management. This advancement was found effective in reducing the harmful effects of Staphylococcus epidermidis, a common bacterium associated with hospital infections and antibiotic resistance. In both studies, researchers employed charged ions to influence bacterial behavior.
“As effective antibiotics become scarce, their widespread use over the years has contaminated environments worldwide, from the Arctic to our oceans and groundwater,” warned Süel. “There is a pressing need for drug-free alternatives to treat bacterial infections, and our recent studies demonstrate that such control over antibiotic-resistant bacteria is achievable without drugs.”
The study’s authors include Eun Chae Moon, Tushar Modi, Dong-yeon Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan, and Gürol Süel.
