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Beating the bacteria


With the rise of antibiotic resistance, researchers are constantly seeking new approaches to keep one step ahead in the fight against bacterial infections. Many cellular processes and molecular structures are similar between humans and bacteria but there are differences. These differences are the best targets to explore as they should allow drugs to be developed that are specific to bacteria without interfering with the normal functioning of the humans and animals they aim to protect.


In cells from bacteria to humans, energy from the metabolism of nutrients is held in a chemical called adenosine triphosphate (ATP). ATP is produced by a protein called ATP synthase, a complex enzyme that rotates like a biological motor to add a phosphate onto adenosine diphosphate (ADP) to make ATP. When energy is needed to power cellular processes, ATP is converted back to ADP by removal of a phosphate group, which releases energy.

ATP synthase uses a rotary catalytic mechanism, whereby rotation of a central axel confers shape changes within the protein that facilitate chemical reactions. Researchers from the Victor Chang Cardiac Research Institute, UNSW Sydney and collaborators in New York and Oxford have now determined the 3D structures of the different shapes that ATP synthase adopts as it carries out different activities. Amongst the various structures, they observed that one is unique to bacteria. This is a region of the protein that can flip into a position that stops the enzyme from functioning. This occurs to save resources when the bacteria are under stress. However, this mechanism could potentially be highjacked by drug designers to switch off the enzyme permanently, killing the bacteria.

The protein structures revealed by this research are the first to be determined using the recently acquired cryo TEM at the Microscopy Australia facility at UNSW Sydney.


This new knowledge will:

  • inform antibacterial drug design, potentially saving millions of lives
  • provide insights into potential functional designs for bionanotechnology components.

Ref. M. Sobti et al., 2019, eLife 2019;8:e43864. DOI:


November 27, 2019