Researchers at the Massachusetts Institute of Technology report that intelectin-2, a carbohydrate-binding lectin found in the gastrointestinal tract, can both crosslink mucus components to reinforce the gut’s protective barrier and bind certain bacteria, restricting their growth and reducing viability—findings that may inform future approaches to drug-resistant infections and inflammatory bowel disease.
The moist surfaces that line the body—including the gastrointestinal (GI) tract—contain molecules that help defend against microbes and limit infection and inflammation. Among them are lectins, a large family of carbohydrate-binding proteins that recognize sugar molecules on the surfaces of cells and microbes.
In a study led by Laura L. Kiessling at the Massachusetts Institute of Technology (MIT), researchers focused on a lectin called intelectin-2 and found it can protect the gut in two ways. First, intelectin-2 binds the sugar galactose, which is commonly found in mucins—the molecules that form mucus. By binding to galactose on mucins, intelectin-2 can crosslink mucin components and strengthen the mucus layer that helps protect the intestinal lining.
Second, the team reported that galactose-containing carbohydrates can also appear on the surfaces of some bacteria. In laboratory tests described by the researchers, intelectin-2 attached to microbes displaying these sugars, trapping them and slowing their growth. Over time, the trapped microbes began to break apart—an observation the researchers say is consistent with disruption of bacterial membranes and a loss of viability.
The researchers said intelectin-2 showed activity against a range of bacteria, including the pathogens Staphylococcus aureus and Klebsiella pneumoniae, which can be difficult to treat when they acquire resistance to standard antibiotics.
The work also highlights differences in where intelectin-2 is produced across species. In humans, the researchers report that intelectin-2 is constitutively produced by Paneth cells in the small intestine. In mice, they report that intelectin-2 is produced by mucus-secreting goblet cells in response to inflammation or certain parasitic infections.
Kiessling, the Novartis Professor of Chemistry at MIT and the study’s senior author, said intelectin-2 “operates in two complementary ways,” helping stabilize the mucus layer while also neutralizing or restraining bacteria if that barrier is compromised. She also said that “harnessing human lectins as tools to combat antimicrobial resistance” could offer a different strategy that draws on innate immune defenses.
The researchers also pointed to inflammatory bowel disease as a potential area for future investigation. They said intelectin-2 levels can be unusually low or unusually high in people with inflammatory bowel disease, and that either imbalance could be harmful—low levels potentially weakening the mucus barrier and high levels potentially eliminating beneficial gut bacteria. They suggested that therapies aimed at restoring balanced intelectin-2 levels could be worth exploring.
The paper, published in Nature Communications, lists Amanda E. Dugan and Deepsing Syangtan as lead authors and Kiessling as senior author. The work was funded by the National Institutes of Health’s Glycoscience Common Fund, the National Institute of Allergy and Infectious Disease, the National Institute of General Medical Sciences, and the National Science Foundation.
