A new study shows for the first time the influence of ion flow on the survival of some bacteria against a type of antibiotic. The results provide a new vision for the study of new drugs or even increase the effectiveness of those currently used.

The antibiotics are our main strategy to fight bacterial infections. But sometimes, when we apply an antibiotic to a population of bacteria, not all of them are eliminated. Even in cases where all microbes are genetically identical, have not developed resistance to the antibiotic and are in equal conditions, some survive and others do not.

Scientists at Pompeu Fabra University and the University of California – San Diego (UCSD) have discovered that this situation is caused by magnesium, which promotes the survival of some bacteria against a type of antibiotic. In this work, published in the journal Cell, the influence of ion flow on such survival is shown for the first time.

Researchers have studied antibiotics that fight against bacteria by blocking their protein manufacture. That is, they attack ribosomes, the molecular machinery responsible for the production of proteins within cells and, therefore, one of the fundamental pillars for bacterial growth.

Ribosomes maintain their complex structure thanks to the presence of ions, electrically charged molecules. The scientists observed that the ions that have a more important role in the structure of the ribosome are those of magnesium, since they are united to these, they contribute cohesion to them and thus they stabilize them.

“When we attack ribosomes with antibiotics, if they have enough magnesium they are more stable and, therefore, more resistant“, explains Jordi Garcia-Ojalvo, Professor of Biology Systems at the UPF Department of Experimental and Health Sciences (DCEXS). “In contrast, when bacteria have little magnesium, their ribosomes are more unstable and when they are attacked they destabilize, the cell cannot produce proteins correctly and it dies,” Garcia-Ojalvo adds.

Study of new antibiotics

Letícia Galera-Laporta, first author of the study, explains that “to demonstrate that the main factor that determines the survival of Bacillus subtilis bacteria   is the regulation of magnesium, we combine the study of a mathematical model and experiments, among which are included different chemical and structural perturbations of ribosomes.”

Despite the difficulty of measuring the concentration of magnesium at individual cells, they could obtain this data by measuring the membrane potential of millions of cells using fluorescence microscopy.

The membrane potential is present in all cells, for example in the neurons of our brain, and is associated with the difference of ions between the inside and the outside of the cell.

This property allowed scientists to detect two types of cells within the same population. A fraction of cells presents sudden changes in the membrane potential, since they do not regulate the flow of ions through their membrane correctly, and finally they end up dying. On the other hand, the cells that under the stress of the antibiotic manage to modulate the flow of magnesium ions and maintain their stable membrane potential are those that survive the attack.

“Our results provide a new vision for the study of new antibiotics or even to increase the effectiveness of the antibiotics currently used. A possible line of future research, for example, could be to use the antibiotic together with a supplement that blocks the transport of magnesium in bacteria,” concludes Galera-Laporta.

 

Source: SINC