MIT Researchers Uncover How Mucins Block Salmonella Infection

MIT researchers have uncovered how natural mucus molecules known as mucins help the body fight infections and defend against Salmonella and other bacteria that cause diarrhea. In their study published in Cell Reports, the team showed that specific mucins can turn off genes that Salmonella enterica uses to invade host cells, suggesting a path toward developing synthetic mucins to prevent gastrointestinal infection.

Mucus line much of the body and serve as more than a protective barrier; they actively interfere with pathogens. One mucin, MUC2, found in the intestines, was shown to silence genes needed by Salmonella to produce the type 3 secretion system (T3SS), which normally allows the bacteria to inject proteins into host tissues. “By using and reformatting this motif from the natural innate immune system, we hope to develop strategies to preventing diarrhea before it even starts. This approach could provide a low-cost solution to a major global health challenge that costs billions annually in lost productivity, health care expenses, and human suffering,” said study senior author Katharina Ribbeck.

Lead authors Kelsey Wheeler and Michaela Gold investigated how mucins interfere with bacterial regulators. Their work revealed that MUC2 blocks HilD, a protein needed to trigger virulence genes encoded in Salmonella pathogenicity island 1 (SPI-1). Computer modeling showed that sugars within the glycans of MUC2 can bind to HilD, but only when linked to the mucin’s peptide backbone, making the complete structure essential for its protective effect.

The researchers also studied MUC5AC, a mucin found in the stomach, and found that it inhibits HilD as well. Both MUC2 and MUC5AC prevented virulence pathways in Salmonella and in other foodborne pathogens that rely on HilD regulation. These findings expand on Ribbeck’s prior work showing that mucins can contain other harmful microbes, such as Vibrio cholerae, Pseudomonas aeruginosa, and Candida albicans.

Looking forward, the team envisions creating synthetic mucins that mimic these natural defenses. Areas of the gastrointestinal tract with thin or absent mucus barriers are especially vulnerable, and adding mucin-like molecules could provide new protection. Wheeler explained, “Part of Salmonella’s evasion strategy for this host defense is to find locations where mucus is absent and then infect there.” Future applications could include mixing synthetic mucins with oral rehydration salts or developing chewable tablets for travelers at risk of exposure. As Wheeler emphasized, “Mucin mimics would particularly shine as preventatives, because that’s how the body evolved mucus—as part of this innate immune system to prevent infection.”