Study finds new avenue to target bacterial infections

Monday 5 November 2018

An international research team including ANU has found a potential new avenue to one day stop potentially harmful bacterial infections by switching off the bacteria's ability to replicate itself.

In this new study, led by Stockholm University in Sweden, the researchers discovered a new type of enzyme that is found in certain types of bacteria responsible for urinary tract infections and bacterial pneumonia.

All organisms - from humans to bacteria - have this enzyme, called ribonucleotide reductase (RNR), which makes the building block units used to create DNA. In most cases, RNR requires metals to function, but this new family of RNR enzymes does not use metals.

ANU researcher Dr Nick Cox said one general strategy that the immune system uses to fight invading bacteria was to starve them of metals.

"Many of the bacteria that use this newly discovered group of RNR are pathogens that invade mucosal surfaces in the respiratory system and genitalia," said Dr Cox from the ANU Research School of Chemistry.

He said the research into this enzyme was still in the early stages, and further work would need to be done to develop a potential new treatment for these types of bacterial infections.

"This discovery should, in the future, allow researchers to develop new drugs that target this new form of RNR - killing the bacterial infection by switching off the bacteria's ability to make DNA and, in turn, replicate," Dr Cox said.

He said these bacteria were often difficult to treat using current therapies. In particular, bacteria from the family mollicutes - which are very small bacteria (1/10,000 of a millimetre in length) - use this new type of RNR exclusively and lack a cell wall, which is a target for many antibiotics.

This study used several techniques to reveal the structure and function of this new RNR enzyme, including: x-ray crystallography, mass spectrometry and electron paramagnetic resonance (EPR) spectroscopy, which creates a three-dimensional structure of a molecule. Dr Cox analysed the EPR spectroscopic data.

ANU is establishing a new state-of-the-art EPR facility, with support from the Australian Research Council (ARC), University of New South Wales, University of Queensland, University of Sydney and University of Wollongong.

"This new facility will operate at much higher magnetic fields than what is currently available, allowing more detailed measurements to be performed," Dr Cox said.

"The new facility will not only enable biochemical and medical research, as in the study described, but also research in the chemical and materials fields, along with industrial applications." 

This study was a collaboration between researchers at Stockholm University and Karolinska Institute in Sweden, the Max Planck Institute in Germany, ANU and Stanford University of the United States.

The study is published in Nature: http://dx.doi.org/ 10.1038/s41586-018-0653-6

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