Breakthrough will aid the fight against deadly bacteria and help to develop new cures

Using some of the world’s most powerful microscopes, three international research teams – from Australia, the Czech Republic and a German/US/Finnish consortium – have discovered a unique molecular mechanism that allows pathogenic bacteria to maintain efficient gene expression.

The new insights are published in back-to-back articles in Nature Communications, a leading scientific journal.

One of the tiny machines that operates inside our cells, keeping all living things alive, is called RNA polymerase (RNAP). RNAP reads the genetic code in our DNA and transcribes it into another molecule called RNA that carries out other vital functions, such as producing the proteins that keep us alive.

Every so often, RNAP gets “stuck” on DNA while it is transcribing it into RNA. This creates two problems: First, that particular RNAP goes out of commission, but more importantly, if DNA replication takes place and the DNA replication machinery hits such a stuck RNAP, it may result in all sorts of problems and may ultimately lead to cell death.

Using cryogenic electron microscopy (Cryo-EM), a powerful approach that can resolve the 3D structures of macromolecular complexes to high resolution, the researchers were able to see how some bacteria solve this fundamental problem.

The Australian team, headed by Dr Gökhan Tolun from UOW and Professor Peter Lewis from the University of Newcastle, studied the HelD complex of RNAP from an important model bacterium, Bacillus subtilis, closely related to dangerous human pathogens such as Bacillus anthracis (anthrax) and Clostridium difficile (lethal pseudomembranous colitis and diarrhea).

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