The findings could reveal an important target for new drugs to tackle numerous infectious diseases in humans.
The nutrient, called ergothioneine, or EGT, was found to protect bacteria from oxidative stress—an imbalance in the body between reactive oxygen species, known as free radicals, and antioxidants—which is a hallmark of many disease-causing infections.
Oxidative stress occurs when immune cells produce oxygen-containing free radicals to kill harmful bacteria. Under these circumstances, bacteria rely on antioxidant molecules, which counteract the free radicals generated by the immune system, to survive.
Despite decades of research, the specific molecules used by certain bacteria to shield themselves from free radicals in our bodies have remained a mystery.
The new findings in the journal Cell offer important clues.
In the study, researchers at the Yale University Microbial Sciences Institute found that bacteria ingest the EGT nutrient—which is abundant in foods like mushrooms, beans, and grains—to aid their survival. In the case of the gastric cancer-causing pathogen Helicobacter pylori, the bacterium used the nutrient to compete successfully for survival in host tissues.
While similar studies have looked to the field of genetics, for the new study, the researchers detected bacterial EGT uptake using mass spectrometry and a novel technique they call “reactivity-guided metabolomics”—which harnesses the unique chemistry of specific classes of molecules to identify them in complex biological settings.
“We were excited to discover an unconventional mechanism that enables bacteria to withstand oxidative stress during infection,” says senior author Stavroula Hatzios, an assistant professor of molecular, cellular, and developmental biology, and of chemistry.
“Because the protein that bacteria use to take up EGT operates in a manner distinct from that of its counterpart in human cells, we are optimistic that a specific drug could be developed to inhibit microbial uptake of this nutrient,” she adds.
Human cells also take in dietary EGT. In humans, EGT is known for its anti-inflammatory properties and is widely associated with disease prevention.
Reduced levels of EGT have been linked to increased risk of neurodegenerative, cardiovascular, and autoimmune disorders, suggesting bacterial consumption of this nutrient may have far-reaching implications for human health.
Additional coauthors are from Tufts University, the Dana-Farber Cancer Institute, and Yale.
Source: Jon Atherton for Yale University
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