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UMSOD Researcher Studies How Bacterial Components Lead to Septic Shock

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Written by Adam Zewe

The body's immune system is programmed to seek and destroy harmful bacteria. Sometimes, that immune response is so vigorous that the body goes into septic shock, which is a serious medical condition that can lead to organ failure. Robert Ernst, PhD, associate professor in the Department of Microbial Pathogenesis, has conducted a collaborative research project to better understand how one component of bacteria, lipopolysaccharide (LPS), can contribute to septic shock.

Ernst and senior author Edward A. Miao, MD, PhD, assistant professor in the Department of Microbiology and Immunology at the University of North Carolina at Chapel Hill, recently published their findings in the journal Science. Their paper, entitled "Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock," explained how LPS, which is the fatty outer shell of bacteria, can kick-start an immune system response that leads to septic shock.

All Gram-negative bacteria synthesize their own unique LPS molecules. When the bacteria enter the body, these LPS molecules are typically recognized by specific components of the body's immune system, known as Toll-like receptor (TLR) 4."TLR4 is one of our front line surveillance systems, but sometimes bacteria can get past the front line and into the cell," remarks Ernst. Once LPS enters the cell, it triggers the body's immune response by stimulating the activity of the enzyme caspace-11. This caspace-11 activity initiates cell death and causes the body to push the immune system into overdrive, which leads to septic shock.

Septic shock is often a devastating condition for patients, even though it is caused by the body's natural defenses. Once a patient has a high level of LPS in his or her bloodstream, the body's increased production of certain immune-system chemicals can lead to severely low blood pressure, as well as damage to the heart and blood vessels. According to the Centers for Disease Control, septic shock is the 13th leading cause of death in the United States.

By studying the structure and function of LPS, Ernst hopes to develop a better understanding of how these bacterial components trigger the caspace-11 process. Future studies will seek to unlock the puzzle of what actually happens within the cell once LPS signals the start of caspace-11. "If we can understand this pathway, how LPS activates caspace-11, maybe there is a way to turn down the immune system response so the patient doesn't enter septic shock," Ernst says.

Ernst is excited about the implications of this research project. Future studies could lead to the development of effective new treatments for severely ill patients. "Many patients who go through septic shock die or have reduced mental functions due to inflammation. Any treatment that could at least dampen the immune system response could give them a better quality of life after their infection," Ernst concludes.

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