Magnesium-Focused Approach to Curbing Antibiotic Resistance

According to recent estimates, the number of fatal antibiotic-resistant illnesses is expected to increase significantly over the next 25 years. According to a recent study, drug-resistant diseases caused over one million fatalities between 1990 and 2021, and by 2050, new estimates indicate that number will have risen to around two million deaths annually.

Scientists are searching the complex physics of bacterial infection for novel ways to combat this public health emergency. A weakness in antibiotic-resistant bacterial strains has been found by researchers at the University of California, San Diego.

The antibiotic resistance of Bacillus subtilis was examined by Professor Gürol Süel and associates at UC San Diego's School of Biological Sciences in collaboration with labs at Arizona State University and the Universitat Pompeu Fabra (Spain).

The question of why after developing an antibiotic-resistant advantage, mutant forms of bacteria do not multiply and take over the population served as the impetus for their investigation. These bacteria should become prevalent since they have an advantage over other bacteria that do not have the same level of antibiotic resistance. But they are not. Why?

According to a study published in the journal Science Advances, the answer is that antibiotic resistance has a price. The scientists found that antibiotic resistance is associated with a physiological constraint that prevents potential dominance, even though it gives the bacteria certain benefits to live. The researchers point out that this finding might be used to prevent the spread of antibiotic resistance.

We discovered an Achilles heel of antibiotic-resistant bacteria. We can take advantage of this cost to suppress the establishment of antibiotic resistance without drugs or harmful chemicals.”

Gürol Süel, Professor, Department of Molecular Biology, University of California San Diego

All living cells, including bacterial cells, have spontaneous DNA mutations. Antibiotic resistance is a result of some of these mutations. Süel and his associates concentrated on physiological processes involving ribosomes, which are tiny machines found in cells that are essential for translating genetic information and building proteins.

For survival, all cells need charged ions like magnesium ions. Magnesium ions are necessary for ribosomes because they stabilize their structure and function. However, the new study's atomic-scale modeling revealed that mutant ribosome variations that confer antibiotic resistance compete for magnesium ions with ATP molecules, which give living cells their energy.

Additionally, mathematical models demonstrated that this leads to a tug-of-war between ATP and ribosomes over the cell's limited supply of magnesium.

Researchers who studied the “L22” ribosome variation in Bacillus subtilis discovered that competition for magnesium inhibits L22's growth more than it does for a typical “wild type” ribosome that is not antibiotic-resistant. As a result, the rivalry causes a physiological cost associated with resistant mutant bacteria.

While we often think of antibiotic resistance as a major benefit for bacteria to survive, we found that the ability to cope with magnesium limitation in their environment is more important for bacterial proliferation.”

Gürol Süel, Professor, Department of Molecular Biology, University of California San Diego

Without the use of medications or hazardous chemicals, this recently identified vulnerability can now be targeted to combat antibiotic resistance. By chelating magnesium ions from bacterial habitats, for instance, it would be feasible to selectively kill resistant types of bacteria without affecting the wild-type bacteria which could be good for human health.

We show that through a better understanding of the molecular and physiological properties of antibiotic-resistant bacteria, we can find novel ways to control them without the use of drugs.”

Gürol Süel, Professor, Department of Molecular Biology, University of California San Diego

Süel and associates at the University of Chicago unveiled a different strategy in October to address the health crisis caused by antibiotic-resistant bacteria. Another drug-free method of treating infections is made possible by their creation of a bioelectronic device that uses the electrical activity of some bacteria that are naturally present on the skin.

It has been demonstrated that the development lessens the negative impacts of Staphylococcus epidermidis, a common bacterium that contributes to antibiotic resistance and causes hospital-acquired illnesses. The researchers employed charged ions to manage the microorganisms in both investigations.

Süel said, “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. 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.”