Scientists Discover Natural Protein That Traps and Kills Harmful Bacteria

Researchers have uncovered how a gut protein both strengthens mucus and restrains bacteria, revealing a potential new strategy for protecting the intestine from infection and inflammation. Credit: Shutterstock On left, mltln2 stabilizes the mucus layer on healthy tissue. On right, it neutralizes bacteria in an inflamed GI tract. Credit: Courtesy of the researchers The protein called intelectin-2 plays another important role by reinforcing the protective mucus layer that lines the digestive system. The body’s mucosal linings contain a range of protective molecules that help stop microbes from triggering inflammation or infection. One important group of these defenders is lectins, which identify microbes and other cells by attaching to sugars on their surfaces. MIT researchers report that one lectin can act against many types of bacteria in the gastrointestinal (GI) tract. The protein, called intelectin-2, latches onto sugars on bacterial membranes, which helps trap the microbes and slows their growth. It also links together components of mucus, a step that can reinforce the mucus barrier. “What’s remarkable is that intelectin-2 operates in two complementary ways. It helps stabilize the mucus layer, and if that barrier is compromised, it can directly neutralize or restrain bacteria that begin to escape,” says Laura Kiessling, the Novartis Professor of Chemistry at MIT and the senior author of the study. Because intelectin-2 appears to work broadly against gut bacteria, the researchers say it could be developed into a therapeutic approach. They also suggest it might be used to bolster the mucus barrier in conditions such as inflammatory bowel disease. Amanda Dugan, a former MIT research scientist, and Deepsing Syangtan PhD ’24 are the lead authors of the paper, which was recently published in Nature Communications . A multifunctional protein Current evidence suggests that the human genome encodes more than 200 lectins - carbohydrate-binding proteins that play a variety of roles in the immune system and in communication between cells. Kiessling’s lab, which has been exploring lectin-carbohydrate interactions, recently became interested in a family of lectins called intelectins. In humans, this family includes two lectins, intelectin-1 and intelectin-2. Those two proteins have very similar structures, but intelectin-1 is distinctive in that it only binds to carbohydrates found in bacteria and other microbes. About 10 years ago, Kiessling and her colleagues were able to discover intelectin-1’s structure, but its functions are still not fully understood. At that time, scientists hypothesized that intelectin-2 might play a role in immune defense, but there hadn’t been many studies to support that idea. Dugan, then a postdoc in Kiessling’s lab, set out to learn more about intelectin-2. Linking mucus and microbes In humans, intelectin-2 is produced at steady levels by Paneth cells in the small intestine, but in mice, its expression from mucus-producing Goblet cells appears to be triggered by inflammation and certain types of parasitic infection. In the new study, the researchers found that both human and mouse intelectin-2 bind to a sugar molecule called galactose. This sugar is commonly found in molecules called mucins that make up mucus. When intelectin-2...

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