Recent estimates indicate that deadly antibiotic-resistant infections will increase rapidly over the next quarter century. More than 1 million people died each year from drug-resistant infections between 1990 and 2021, a recent study reported, with new projections rising to nearly 2 million deaths each year by 2050.
In an effort to counter this public health crisis, scientists are searching for new solutions within the intricate mechanics of bacterial infection. A study led by researchers at the University of California, San Diego has discovered a vulnerability in antibiotic-resistant strains of bacteria.
Working with laboratories at Arizona State University and Pompeu Fabra University (Spain), Professor Gürol Süel and colleagues at UC San Diego’s School of Biological Sciences investigated the bacteria’s antibiotic resistance. Bacillus subtilis. Their research was motivated by the question of why mutant variants of bacteria do not proliferate and take over the population once they have developed an antibiotic-resistant lead. With an advantage over other bacteria that lack similar antibiotic resistance, such bacteria should become dominant. However, they are not. Because?
The answer, published in the magazine. Scientific advancesis that antibiotic resistance has a cost. While antibiotic resistance provides some advantages for bacteria to survive, the team found that it is also related to a physiological limitation that hinders potential dominance. This fact, the researchers note, could potentially be exploited to stop the spread of antibiotic resistance.
“We discovered an Achilles’ heel of antibiotic-resistant bacteria,” said Süel, a member of the Department of Molecular Biology at UC San Diego. “We can leverage this cost to suppress the establishment of antibiotic resistance without harmful drugs or chemicals.”
Spontaneous DNA mutations arise in all living cells, including those of bacteria. Some of these mutations lead to antibiotic resistance. Süel and his colleagues focused on physiological mechanisms related to ribosomes, the micromachines inside cells that play a key role in protein synthesis and the translation of genetic codes.
All cells depend on charged ions, such as magnesium ions, to survive. Ribosomes depend on magnesium ions, as this metal cation helps stabilize their structure and function. However, atomic-scale modeling during the new research found that mutant ribosome variants that confer antibiotic resistance excessively compete for magnesium ions with adenosine triphosphate (ATP) molecules, which provide energy to power cells. alive Mathematical models further showed that this results in a tug-of-war between ribosomes and ATP for a limited supply of magnesium in the cell.
Studying a ribosome variant within bacillus subtilis Called “L22,” the researchers found that competition for magnesium hinders the growth of L22 more than a normal “wild-type” ribosome that is not resistant to antibiotics. Therefore, competition imposes a physiological cost related to mutant bacteria with resistance.
“Although we often think of antibiotic resistance as an important benefit for bacterial survival, we found that the ability to cope with magnesium limitation in their environment is more important for bacterial proliferation,” Süel said.
This newly discovered weakness can now be used as a target to counteract antibiotic resistance without the use of drugs or toxic chemicals. For example, it may be possible to chelate magnesium ions from bacterial environments, which should selectively inhibit resistant strains without affecting wild-type bacteria that may be beneficial to our health. “We show that through a better understanding of the molecular and physiological properties of antibiotic-resistant bacteria, we can find new ways to control them without the use of drugs,” Süel said.
In October, Süel and his colleagues at the University of Chicago announced a separate approach to combat the health crisis of antibacterial-resistant bacteria. Their development of a bioelectronic device that harnesses the natural electrical activity of certain bacteria found on our skin paves the way for another drug-free approach to controlling infections. The breakthrough was shown to reduce the harmful effects of Staphylococcus epidermidisa common bacteria known to cause hospital-acquired infections and contribute to antibiotic resistance. In both studies, the researchers used charged ions to control the bacteria.
“We are running out of effective antibiotics and their rampant use over decades has caused antibiotics to spread around the world, from the Arctic to the oceans and our groundwater,” Süel said. “Non-drug alternatives are needed to treat bacterial infections and our two most recent studies show how we can achieve drug-free control over antibiotic-resistant bacteria.”
The authors of the new study were: Eun Chae Moon, Tushar Modi, Dong-yeon Lee, Danis Yangaliev, Jordi García-Ojalvo, S. Banu Ozkan and Gürol Süel.