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Researchers Harness Bacterial Stealth Strategy to Fight Inflammation

New Study in Cell Host & Microbe Could Lead to New Treatments for Inflammatory Diseases Such as Arthritis, Emphysema and Colitis

Contact: Sally Stewart | Email: sally.stewart@cshs.org

Los Angeles - Dec. 10, 2015 - In their quest to find new therapies for patients with inflammatory diseases, Cedars-Sinai investigators have discovered a powerful strategy employed by bacteria that could be used to develop new inflammation-fighting treatments.

In the December issue of Cell Host & Microbe, the researchers explain that bacteria face many of the same inflammatory challenges with infections as humans face with inflammatory diseases such as diabetes, rheumatoid arthritis and pulmonary emphysema. As a result, bacteria develop anti-inflammatory strategies of their own to stay alive in the human body.

"This study suggests that bacteria’s own tools to survive infection in the human body could potentially be used as therapeutic agents for many inflammatory diseases," Stacey Kolar, PhD, first author of the study.

The findings represent an important step in ongoing efforts to develop effective treatments for inflammatory diseases that affect millions worldwide. Current treatments for Crohn’s disease, hepatitis and other inflammatory conditions are aimed at diminishing symptoms but may not address the root cause or prompt inflammation to subside.

Central to the new finding is a sugar molecule called hyaluronan. This molecule, found in most human tissues, lubricates joints and can be used as a filler for sagging, aging skin.

The immune system fights infection by relying on a specific enzyme to break down hyaluronan into fragments which signal to the immune system that the body is under attack and to crank up inflammation.

The investigators found that many bacteria produce a different version of the enzyme that destroys the sugar molecule fragments.

"By doing so, the bacterial enzyme prevents the immune system from turning up inflammation," said George Liu, MD, PhD, senior author of the study and a pediatric infectious diseases physician at Cedars-Sinai’s Maxine Dunitz Children’s Health Center and the F. Widjaja Inflammatory Bowel and Immunobiology Research Institute.

When the sugar molecule fragments are broken down by bacteria, substances called hyaluronan disaccharides further block inflammatory responses by the immune system.

"The net result is that the bacteria have developed a powerful way to shut down inflammation and evade detection," Liu said.

Because hyaluronan disaccharides and bacterial enzymes that degrade the sugar molecule both uniquely dampen the immune system, the investigators tested whether the same strategy could be used to block inflammation in the lungs of laboratory mice.

"What we saw was a complete absence of inflammation when lung tissues were inspected under the microscope," Kolar said. "Treatment with the disaccharides or with the bacterial enzyme dramatically dampened markers of inflammation."

In future studies, the researchers plan to test their new therapeutics against an array of human inflammatory diseases.

The study was supported by a Burroughs-Wellcome Career Award and a National Institutes of Health research grant under award number T32 AI89553-3 and AI 10383-9.

From left to right: A view of a normal lung with open air sacs, an inflamed lung with reduced air sacs
and a treated lung with open air sacs.