Human Gene for Key Sepsis Protein (Gasdermin-D) Identified; Cleavage of GSDMD Triggers Cell Daath by Pyroptosis; Discovery May Lead to More Effective Treatments of Often-Lethal Whole-Body Infection Condition, and Also of Other Inflammatory Disorders

Scientists have identified a gene that could potentially open the door for the development of new treatments of the lethal disease sepsis. Researchers from The Australian National University (ANU) and the Garvan Institute of Medical Research worked with Genentech, a leading United States biotechnology company, to identify a gene that triggers the inflammatory condition that can lead to the full-body infection sepsis. "Isolating the gene so quickly was a triumph for the team," said Professor Simon Foote, Director of The John Curtin School of Medical Research (JCSMR) at ANU. Sepsis is a severe whole-body infection that kills an estimated one million people in the United States alone each year. It occurs as a complication to an existing infection, and, if not treated quickly, can lead to septic shock and multiple organ failure, with death rates as high as 50 per cent. Professor Foote acknowledged the vital support of the Australian Government's National Collaborative Research Infrastructure Strategy in setting up the Australian Phenomics Facility at JCSMR, where the gene was identified. Researchers were aware that sepsis occurs when molecules known as lipopolysaccharides (LPS) on the surface of gram-negative bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct. But exactly how the self-destruct button was pressed had remained a mystery, until now. The team found that the protein gasdermin-D (image) plays a critical role in the pathway to sepsis. Scientists at Genentech showed that gasdermin-D usually exists in cells in an inactive form.