An antibiotic resistance study has revealed a previously unknown bacterial survival mechanism. According to the study, which was conducted by scientists based at the University of California, San Diego (UCSD), bacteria defend themselves against antibiotics by boosting their intake of magnesium, which bacteria can use to shield their ribosomes, their protein-synthesizing machinery, from harm.
Exposing this mechanism is a little like finding a chink in the bacterial armor. Exploiting this chink could increase the effectiveness of ribosome-targeting antibiotics.
“With this discovery,” asserted the study’s leader, Gürol Süel, PhD, professor, molecular biology at UCSD, “we can now explore new ways to combat infections that we couldn’t have thought of before.”
Curiously, the newly discovered mechanism promotes the survival of actively growing bacteria. Antibiotic resistance is usually thought to be achieved by bacteria that enter “dormant” nongrowing states.
Detailed findings from the study appeared March 7 in the journal Cell, in an article titled, “Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival.” The article describes how Süel’s team investigated the relationship between ribosomal activity and the electrochemical flux of ions across cell membranes. Membrane potential modulation and ribosomal activity are among the most ancient and fundamental processes that operate in all living cells, from bacteria to humans.
“Specifically, we 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,” wrote the article’s authors. “Using structural perturbations of the ribosome and proteomic analysis, we uncovered that stress resilience arises from magnesium influx, which prevents hyperpolarization.”
These findings reveal how ion flux modulation and ribosomal activity—two ancient and fundamental cellular processes that are essential for life—interact with each other. They also lay the scientific groundwork for new ways to counteract antibiotic resistance.
“Antibiotic resistance is a major public threat to our health,” noted Süel. “The number of drugs coming onto the market is not keeping up with the ability of bacteria to cope with those drugs.”
Süel 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.