As bacteria continue to demonstrate powerful resilience to antibiotic treatments--posing a rising public health crisis involving a variety of infections--scientists continue to seek a better understanding of bacterial defenses against antibiotics in an effort to develop new treatments.

Now, researchers who combine experiments and mathematical modeling have discovered an unexpected mechanism that allows bacteria to survive antibiotics.

As described in the journal Cell, the researchers discovered that bacteria defend themselves against antibiotics by controlling the uptake of alkaline metal ions. When under attack by antibiotics, bacteria were found to modulate magnesium ion uptake in order to stabilize their ribosomes--the fundamental molecular machines of life that translate genes into proteins--as a survival technique.

"We have found an unexpected new mechanism that actively growing bacteria utilize to become resilient against antibiotics," said the senior author. "With this discovery we can now explore new ways to combat infections that we couldn't have thought of before."

The researchers investigated the relationship between ribosome activity and the electrochemical flux of ions across cell membranes. This membrane potential and ribosomes are among the most ancient and fundamental processes that operate in all living cells, from bacteria to humans. The scientists identified a distinct connection that "reveals how these ancient and fundamental cellular processes that are essential for life are interacting with each other," said the author.

Authors observed two types of cellular behavior: growth-defective cells exhibited a mathematically predicted transient increase in membrane potential (hyperpolarization), followed by cell death, whereas growing cells lacked hyperpolarization events and showed elevated survival. Using structural perturbations of the ribosome and proteomic analysis, they uncovered that stress resilience arises from magnesium influx, which prevents hyperpolarization. Thus, ion flux modulation provides a distinct mechanism to cope with ribosomal stress.
 
The author believes scientists may be able to boost the potency of existing antibiotic drugs by manipulating the ability of bacteria to take up magnesium, rather than having to develop completely new drugs. The potency of certain classes of antibiotics that are used to treat serious infections might be greatly improved by restricting how bacteria take up magnesium, thus interfering with bacteria's ability to use charged magnesium ions in defenses against antibiotics.

https://ucsdnews.ucsd.edu/pressrelease/researchers_discover_a_new_mechanism_used_by_bacteria_to_evade_antibiotics

https://www.cell.com/cell/fulltext/S0092-8674(19)30105-9