Discovery of trigger for bugs' defences could lead to new antibiotics


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Discovery of trigger for bugs' defences could lead to new antibiotics


Date: 21/08/2015

BBSRC-funded scientists at Imperial College London have exposed a chink in the armour of disease-causing bugs, with a new discovery about a protein that controls bacterial defences.

Bacteria react to stressful situations – such as running out of nutrients, coming under attack from antibiotics or encountering a host body’s immune system – with a range of defence mechanisms. These include constructing a resistant outer coat, growing defence structures on the surface or producing enzymes that break down the DNA of an attacker.

The new research shows that a protein called sigma54 holds a bacterium’s defences back until it encounters stress, at which point the protein rearranges its structure to trigger the defences into action. The range of defences that sigma54 controls is so broad that the scientists are moving quickly to learn how to block its action and disable some of the bacteria's armour.

The findings of the study are published today (21 August 2015) in the journal Science by researchers at Imperial College London with collaborators at Peking University in China, Pennsylvania State University and University of Wisconsin-Madison, in the USA.

Scientists already knew of sigma54’s existence but in the new research, the team used the UK's national synchrotron facility – Diamond Light Source, based in Oxfordshire – to explore sigma54’s structure and function in minute detail.

A cellular machine called RNA polymerase (RNAP) is essential for enabling bacteria to function. In the study, the team used the advanced capabilities at Diamond’s Membrane Protein Laboratory to see for the first time how sigma54 directs RNAP to sit on the bacterial DNA, where it is poised to build the bacteria’s defences.

The RNAP-sigma54 complex can only work when it is activated and the scientists have long been trying to find out how sigma54 keeps RNAP in check, at a molecular level. They hope that ultimately, understanding how RNAP is controlled could lead to new ways of disabling bacterial defence mechanisms, and to new compounds that can kill bacteria.

Lead author Professor Xiaodong Zhang, from the Centre for Structural Biology and Department of Medicine at Imperial College London, said: "Bacteria are increasingly developing resistance to antibiotics and with the rise of resistant strains of diseases like tuberculosis, we desperately need to find new ways of tackling this problem.

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Source: BBSRC

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