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New research identifies bacterial ‘Jekyll and Hyde’ molecule involved in immune responses

Structures of 3'cADPR (left) and the Thoeris defence system in complex with 3'cADPR (right)
Structures of 3’cADPR (left) and the Thoeris defence system in complex with 3’cADPR (right)

Griffith University researchers have played a key role in investigating a new molecule that protects bacteria against viruses and is associated with bacterial infection of plants.

Dr Thomas Ve, a lead researcher at Griffith University’s Institute for Glycomics and co-senior author on the new Science paper, said bacteria are on the watch for viral infections and have evolved a large repertoire of defence systems to protect themselves.

Mr Eduardo Vasquez Alarcon, Dr Thomas Ve, Dr Tamim Mosaiab and Dr Yun Shi
Mr Eduardo Vasquez Alarcon, Dr Thomas Ve, Dr Tamim Mosaiab and Dr Yun Shi

“Studying such defence systems have in the past led to powerful molecular tools that may one day be used for new treatments of diseases,” Dr Ve said.

The aim of the study was to look at bacterial enzymes that cleave a ubiquitous nucleotide called NAD (nicotinamide adenine dinucleotide) and produce new signalling molecules.

“These signalling molecules take part in a virus defence system called Thoeris,” Dr Ve said.

“Surprisingly, our research shows one of these molecules – called 3’cADPR – is not only an activator of the Thoeris defence system but is also associated with suppression of the immune system in plants.”

The researchers used a suite of structural biology techniques such as nuclear magnetic resonance, cryo-electron microscopy and x-ray crystallography to reveal the chemical structures of these signalling molecules and how they are produced and function.

“We were able create three dimensional snapshots of how they are produced and how they activate the Thoeris defence system,” Dr Ve said.

“Time will tell if this basic research leads to new technologies with the potential to treat or prevent diseases.”

Institute for Glycomics Director Professor Mark von Itzstein AO
Institute for Glycomics Director Professor Mark von Itzstein AO

Institute Director, Professor Mark von Itzstein AO said this fundamental research brings substantial new insight to complex biology.

“This study published in the world-leading journal Science provides atomic level detail of an intricate biological process,” Professor von Itzstein said.

“The study outcomes open up new areas of endeavour that could have significant biological impact.”

Dr Ve’s team worked in collaboration with the groups of Professor Bostjan Kobe at University of Queensland, Professors Aaron DiAntonio and Jeffrey Milbrandt at Washington University, St Louis, USA, Assistant Professor Ming Guo at University of Nebraska-Lincoln, USA, and Professor Murray Grant at the University of Warwick, UK.

Please click for access to the paper.

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