The Achilles heel of antibiotic-resistant bacteria

To combat this public health crisis, scientists are seeking new solutions within the complex mechanisms of bacterial infection. A study led by researchers at the University of California, San Diego has discovered a vulnerability in antibiotic-resistant bacterial strains.

Professor Gülol Xuel of the University of California, San Diego's School of Biological Sciences and colleagues collaborated with labs at Arizona State University and Pompeu Fabra University (Spain) to investigate antibiotic resistance in bacteria. Bacillus subtilis Their research was motivated by the question of why bacterial mutants do not multiply and take over the population once they acquire antibiotic resistance. Such bacteria should become dominant by gaining an advantage over other bacteria that do not have similar antibiotic resistance. But that's not the case. why?

The answer was reported in a magazine scientific progressthat antibiotic resistance comes at a cost. Although antibiotic resistance provides several advantages for bacteria to survive, the research team found that it is also associated with physiological limitations that prevent potential dominance. Researchers say this fact could be exploited to stop the spread of antibiotic resistance.

“We have discovered the Achilles heel of antibiotic-resistant bacteria,” said Schuell, a member of the Department of Molecular Biology at the University of California, San Diego. “We can use this cost to reduce the establishment of antibiotic resistance without the use of drugs or harmful chemicals.”

Spontaneous mutations in DNA occur in all living cells, including cells within bacteria. Some of these mutations also cause antibiotic resistance. Süel and colleagues focused on physiological mechanisms related to ribosomes, intracellular micromachines that play key roles in protein synthesis and translation of the genetic code.

All cells rely on charged ions, such as magnesium ions, to survive. Ribosomes depend on magnesium ions. This is because this metal cation helps stabilize its structure and function. But the atomic-scale modeling in this new study shows that mutant ribosome variants that confer antibiotic resistance compete excessively for magnesium ions with adenosine triphosphate (ATP) molecules, which provide the energy that powers living cells. It turned out that Furthermore, mathematical models showed that this causes a tug-of-war between ribosomes and ATP over the limited intracellular supply of magnesium.

Study of internal ribosome variants Bacillus subtilis The researchers found that the ribosome, called “L22,” is more stunted in its growth by competing for magnesium than the regular “wild-type” ribosome, which is not resistant to antibiotics. Competition therefore imposes physiological damage associated with resistant mutant bacteria.

“While we often think that resistance to antibiotics is a major survival advantage for bacteria, we now know that the ability to cope with magnesium limitations in the environment is more important for bacterial growth. ,” Schuell said.

This newly discovered weakness can now be used as a target to combat antibiotic resistance without the use of drugs or toxic chemicals. For example, it may be possible to chelate magnesium ions from the bacterial environment. This should allow us to selectively inhibit resistant strains without affecting wild-type bacteria that may be beneficial to our health. “We show that by better understanding the molecular and physiological properties of antibiotic-resistant bacteria, we can find new ways to control them without using drugs,” Schuell said. .

In October, Süel and colleagues at the University of Chicago announced a different approach to combating the antibiotic-resistant health crisis. The development of bioelectronic devices that harness the natural electrical activity of certain bacteria present on our skin paves the way for another drug-free approach to managing infections. This advancement has been shown to reduce harmful effects. Staphylococcus epidermidisa common bacterium known to cause nosocomial infections and cause antibiotic resistance. In both studies, researchers used charged ions to control bacteria.

“A shortage of effective antibiotics and decades of rampant antibiotic use have spread them around the world, from the Arctic to the oceans and groundwater,” Schuell said. “Drug-free alternatives to treating bacterial infections are needed, and our two recent studies demonstrate how drug-free control of antibiotic-resistant bacteria can be achieved in practice. It shows.”

The authors of the new study are Eun Chae Moon, Tushar Modi, Dong-yeon Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan, and Gürol Süel.