Search And Destroy: Newly Identified Gut Protein Kills Bacteria

"These findings were completely unexpected," says Lora V. Hooper, Ph.D., instructor of molecular biology and pharmacology. "We initially thought that this protein might be involved in blood vessel formation. What we discovered, though, is that it's a potent killer of bacteria."

Hooper is first author of the study; Jeffrey I. Gordon, M.D., the Dr. Robert J. Glaser Distinguished University Professor and Head of the Department of Molecular Biology and Pharmacology, led the study.

The team identified a protein called angiogenin 4 (Ang4), which belongs to a class of proteins originally believed to be involved in the development of blood vessels that supply tumors with nutrients. The group discovered that Ang4 was released by specific cells, called Paneth cells, located in the intestinal lining.

Because Paneth cells are known to assist the immune system in defending against infection, the team examined Ang4 to determine how it interacts with a variety of different microbes. They found that the protein killed certain kinds of gut microbes and conclude that Ang4 may be part of an arsenal of microbicidal proteins deployed by Paneth cells to help keep gut bacteria from getting too close to the intestinal lining, where they could cause damage or mount an invasion.

Moreover, the researchers were surprised to find production of Ang4 is controlled by a bacterium that makes its home in the intestine. The microbe, called Bacteroides thetaiotaomicron, is a prominent member of the mouse and human gut microbial community. This makes Ang4 unique, as it is the first example of a protein antibiotic whose expression is controlled by friendly intestinal bacteria.

"Robert Frost said it best: 'Good fences make good neighbors,'" Hooper says. "Apparently, one of the functions of normal gut bacteria is to help erect an "electric fence" that protects the internal milieu from microbes we encounter throughout our lives."

The group also discovered that other mouse and human angiogenins, which are produced in other organs, also are able to combat dangerous microorganisms.

"These findings support the notion that the angiogenin family of proteins may represent a critical component of the body's innate defense system," Gordon says.

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Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: A new class of microbicidal proteins involved in innate immunity. Nature Immunology, March 2003.

Funding from the National Institutes of Health, AstraZeneca and the Burroughs-Wellcome Fund supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC Healthcare.