A natural protein may protect the GI tract from infection

Embedded in the body’s mucosal surfaces, proteins called lectins bind to sugars found on cell surfaces. A team led by MIT chemistry professor Laura Kiessling has found that one such protein, intelectin-2, both helps fortify the mucosal barrier and offers broad-spectrum protection against harmful bacteria found in the GI tract. 

Intelectin-2 binds to a sugar molecule called galactose that is found on bacterial membranes, the team found, trapping the bacteria and hindering their growth; the trapped microbes eventually disintegrate, suggesting that the protein is able to kill them by disrupting their cell membranes. It also helps strengthen the intestine’s protective lining by binding to the galactose in the mucins that make up mucus.

“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 Kiessling, who conducted the study with colleagues including Amanda Dugan, a former MIT postdoc and research scientist, and Deepsing Syangtan, PhD ’24.

Because intelectin-2 can neutralize or eliminate pathogens such as Staphylococcus aureus and Klebsiella pneumoniae, which are often difficult to treat with antibiotics, it could someday be adapted as an antimicrobial agent, the researchers say. Restoring desirable levels of intelectin-2 could also help people with disorders such as inflammatory bowel disease, who may have either too little of it (potentially weakening the mucus barrier) or too much (killing off beneficial gut bacteria).

“Harnessing human lectins as tools to combat antimicrobial resistance opens up a fundamentally new strategy that draws on our own innate immune defenses,” Kiessling says. “Taking advantage of proteins that the body already uses to protect itself against pathogens is compelling and a direction that we are pursuing.” 

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