The key to fighting sepsis

Australian and US researchers have identified a gene that triggers the inflammatory condition that can lead to the full-body infection sepsis. The gene’s discovery could potentially lead to the development of new treatments for the deadly disease.

Sepsis is a severe whole-body infection that kills thousands of Australians 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%.

Researchers were aware that sepsis occurs when molecules known as lipopolysaccharides (LPS) on the surface of some bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct. The team discovered that the protein Gasdermin-D played a critical role in this process.

Scientists at US biotech company Genentech showed that Gasdermin-D usually exists in cells in an inactive form. When the LPS molecules enter the cells they trigger an enzyme called caspase-11 — a kind of chemical hatchet — to lop the protective chemical cap off Gasdermin-D, which in turn leads the cells to self-destruct.

Researchers at the Australian Phenomics Facility, located in The John Curtin School of Medical Research at the Australian National University (ANU), proceeded to screen thousands of genes with a large-scale forward genetics discovery platform. In a little over a year, they had isolated the gene that produces Gasdermin-D.

“This finding is a key that could potentially unlock our ability to shut down [sepsis]… before it gets to a life-threatening stage,” said co-author Chris Goodnow from ANU.

“The identification of Gasdermin-D can give us a better understanding not only of lethal sepsis, but also of multiple other inflammatory diseases,” added co-author Dr Nobuhiko Kayagaki, a senior scientist at Genentech.

The study has been published in the journal Nature.

Image caption: Study co-author Linda Fitzgerald works on the multipipettor at the Australian Phenomics Centre. Image credit: Stuart Hay, ANU.

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