Scientists uncover the structure of a bacterial toxin which injects itself into human cells and kills them

Australian researchers have revealed the molecular structure of a cell-killing toxin produced by the bacterium Serratia marcescens.

S. marcescens is commonly involved in hospital-acquired infections – including respiratory diseases, bloodstream and urinary tract infections – and has developed resistance to many commonly used antibiotics.

Researchers discovered the toxin is able to inject itself into and kill a wide range of living cells, including in humans and livestock, insects, and plants.

Serratia marcescens serine protease (Ssp) toxin had already been discovered in previous research, however there was little understanding of its structure and function before now.

This breakthrough could lead to the development of new antimicrobial treatments.

Dr Jason Paxman, one of two lead researchers who wrote the new study in Nature Communication, says that Ssp is a new type of toxin and its design is unlike any others previously known to science.

“Pretend you’ve never seen a syringe before, but someone explains what a syringe does – injects substances into human tissue, then all of a sudden you have a picture of a syringe, and you see the plunger and needle – that’s what this what we’ve done here,” explains Paxman, who is a Research Fellow in Biochemistry at La Trobe University in Australia.

“So now that we actually have the structure of the toxin, we can see how it injects itself into cells to cause disease, and then start designing ways to stop it.”

The team determined the three-dimensional structure of Ssp using X-ray crystallography and identified a specific domain that promotes cell entry. It might also break down protein targets within the cell to cause its death – though more research is needed to confirm this.

Professor Begoña Heras, Head of the Structural Biology and Bacterial Pathogenesis laboratory at the La Trobe Institute for Molecular Science (LIMS), says that by understanding what Ssp looks like scientists can now develop targeted inhibitors of the toxin.

“These inhibitors or antimicrobials may be developed to bind to the part of Ssp responsible for injecting itself into cells,” says Heras, also a lead researcher on the study.

“Serratia has quite high levels of antibiotic resistance and can cause infections in a wide array of hosts, from humans to insects.”

Inhibiting the Ssp toxin would effectively “disarm” S. marcescens and reduce the severity of sickness during infections.