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Bloody hell! The more your immune system works, the worse the diarrhea

DALLAS – May 11, 2020 – A type of E. coli bacteria that causes bloody diarrhea uses an amino acid produced by the body in response to infection to intensify its symptoms, according to a new study from UT Southwestern scientists.

Vanessa Sperandio smiling
Dr. Vanessa Sperandio

The study, to be published this week in Proceedings of the National Academy of Sciences, is the first to identify the role of the arginine receptor (ArgR) in the progression of enterohemorrhagic E. coli O157:H7 (EHEC) infection. A deeper understanding of this relationship could lead to treatments other than the usual therapy for the illness – hydration.

"We found that the bacteria provoke the host's response and then they use an amino acid that the host makes as part of that response as a signal to increase infectivity," says Vanessa Sperandio, Ph.D., professor of microbiology at UTSW and senior author of the study. The pathogen uses the host’s initial slight increase in arginine as a signal to inject a mix of virulence proteins into the cells lining the host's colon, intensifying inflammation, the study found.

"Usually when the arginine level increases, it's a sign your immune system is working to clear the infection," Sperandio says. "We find that the amino acid levels also rise when the host is being abused by the infection."

Sperandio studies the environment in the gut that is teeming with chemical messages. She is especially interested in EHEC, which can sicken people.

Of the many strains of E. coli, most are harmless, including those that routinely live in the human intestinal tract. However, some kinds of E. coli, including EHEC, produce a toxin that can cause stomach cramps, diarrhea (often bloody), and vomiting. EHEC is transmitted to humans primarily by eating contaminated foods, such as raw or undercooked ground meat products and raw milk, vegetables, and sprouts.

The Centers for Disease Control and Prevention estimates that EHEC causes about 95,000 illnesses in the United States each year. Of those, about 5 to 10 percent become life-threatening and can cause the kidneys to shut down.

Arginine is an amino acid that is either naturally made by the body or acquired from food. The researchers ran an experiment to determine whether dietary arginine had any impact on infection, finding that it did not affect amino acid levels or pathogen burden at the site of infection.

"Dietary arginine is absorbed in the small intestine before it can reach the colon, where EHEC infection rages," Sperandio says.

Because mice are unaffected by EHEC, researchers tested a similar pathogen, Citrobacter rodentium, in mouse studies, Sperandio explains.

"C. rodentium infection increases arginine concentration in the colon. Our study indicates that it is the host cells that are creating the increased colonic arginine levels."

The first author of this study is Zelia Menezes-Garcia, a postdoctoral fellow. Other UTSW authors who contributed to this study are Aman Kumar, Sebastian Winter, and Wenhan Zhu. Winter is a W.W. Caruth, Jr. Scholar in Biomedical Research.

The authors report no disclosures.

This study was supported by the National Institutes of Health (grants: AI053067, AI05135, AI077613, AI114511).

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.