MIT researchers discovered that the protein intelectin-2 neutralizes a broad spectrum of bacteria found in the GI tract. This protein functions by binding to sugar molecules on bacterial membranes, trapping and hindering their growth, and also strengthens the mucus barrier lining the digestive tract. This dual functionality suggests potential therapeutic applications, including for inflammatory bowel disease.
Intelectin-2 Stabilizes Mucus & Restrains GI Bacteria
Intelectin-2 strengthens the gastrointestinal tract’s defenses in two key ways. The protein not only crosslinks molecules within mucus, reinforcing the protective barrier, but also directly binds to galactose—a sugar found on bacterial surfaces—effectively trapping microbes. Researchers observed that entrapped bacteria ultimately disintegrate, indicating intelectin-2 disrupts bacterial cell membranes and can kill a broad spectrum of pathogens, even those resistant to common antibiotics. This multifunctional protein exhibits activity against bacteria causing GI infections, including Staphylococcus aureus and Klebsiella pneumoniae. Notably, intelectin-2 is consistently produced by Paneth cells in the human small intestine, and its ability to bind mucins—molecules forming mucus—helps maintain barrier integrity. Disruptions in intelectin-2 levels may contribute to inflammatory bowel disease, suggesting potential therapeutic strategies to restore optimal levels.
Human & Mouse Intelectin-2 Bind to Galactose Sugars
Both human and mouse forms of intelectin-2 demonstrate a binding affinity for the galactose sugar. This sugar is a key component of mucins, molecules that build the protective mucus layer within the gastrointestinal tract, directly strengthening this barrier. Researchers discovered that when intelectin-2 binds to mucins, it reinforces the mucus, creating a more robust defense against potential pathogens. Furthermore, galactose isn’t limited to mucus; it’s also present in carbohydrates on the surfaces of several bacteria. This allows intelectin-2 to bind directly to microbes, including those responsible for gastrointestinal infections, ultimately disrupting their cell membranes and leading to disintegration, and broadening its antimicrobial impact. This dual binding capability – to both mucus and bacteria – highlights the protein’s multifaceted protective role.
“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,”
Laura Kiessling
Broad-Spectrum Activity Against Antibiotic-Resistant Pathogens
Intelectin-2 demonstrates a powerful ability to combat infection through multiple mechanisms. Researchers found the protein binds to galactose, a sugar present in mucins that build the mucus barrier, effectively strengthening it against bacterial invasion. Crucially, it also targets galactose found on bacterial surfaces, trapping microbes and ultimately causing their disintegration by disrupting cell membranes. The dual action—reinforcing the mucus layer and directly neutralizing escaped bacteria—suggests intelectin-2 could be a valuable therapeutic target. Restoring appropriate levels of this protein may also benefit patients with inflammatory bowel disease, where levels are often disrupted.
Potential Therapeutic Role in Inflammatory Bowel Disease
In individuals with inflammatory bowel disease, levels of intelectin-2 can fluctuate, potentially contributing to disease progression. Low levels may weaken the protective mucus barrier of the gut, while excessively high levels could disrupt the balance of beneficial gut bacteria. Restoring appropriate intelectin-2 concentrations represents a potential therapeutic strategy for managing this condition, according to researchers. This protein’s ability to both reinforce the mucus layer and directly control bacterial growth is significant. Intelectin-2 demonstrates broad-spectrum antimicrobial activity, even against bacteria resistant to conventional antibiotics like Staphylococcus aureus and Klebsiella pneumoniae. Exploiting these innate immune defenses could offer a new approach to combatting antimicrobial resistance and bolstering gut health.
