Study reveals new details about how bacterial toxins cause life-threatening colitis

FINDINGSResearch led by scientists from UCLA and Harvard University has uncovered details about how the bacterium Clostridioides difficile causes excessive inflammation in the gut that can lead to potentially deadly colitis. Studying C. difficile toxin A, one of two toxins released by the bacterium, the researchers produced two key findings.They pinpointed which part of the toxic protein can permeate cell membranes to gain entry to cellular structures called endosomes, demonstrating that even fragments of the protein that contain that key segment are capable of accessing endosomes.In addition, they revealed how the toxin molecule causes inflammation, which has been a long-standing mystery because such molecules are generally quickly digested in the gut. The scientists found that toxin A — and surprisingly even fragments of the toxin — can organize DNA into ordered crystalline particles that amplify an immune response by binding to multiple TLR9 receptors, which are normally part of the body’s early detection system for microbial DNA. The findings demonstrate that this mechani sm causes the body’s natural defenses to produce excessive inflammation.BACKGROUNDInfection from C. difficile in the gut can cause life-threatening colitis, with nearly 500,000 cases and 29,000 deaths in the U.S. alone each year, according to the Centers for Disease Control and Prevention.Older patients who have been treated with antibiotics are at particular risk from C. difficile, which is resi...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news