McMaster researchers discover bacteria-killing toxin that could lead to innovation in antibiotics

Researchers at McMaster University have discovered a bacteria-killing toxin that has the potential to open a new pathway of antibiotics.

The study, published in Molecular Cell, was led by John Whitney at the Michael G. DeGroote Institute for Infectious Disease Research. Whitney and Nathan Bullen, a McMaster biochemistry and biomedical sciences graduate student, spent three years studying the bacterial pathogen Pseudomonas aeruginosa. It causes infections such as pneumonia, but the discovery showed it also secretes a toxin that can kill other species of bacteria.

The significance of the discovery is how the toxin kills bacteria, Whitney said. This toxin targets RNA, a molecule found in all living cells that helps turn genetic code into protein.

I don't think there is any known antibiotic that hits RNA in bacteria," Whitney said, adding that that's what makes this discovery exciting.

Most antibiotics used in hospital are made by bacteria, he said.

Mother nature is better at finding out ways to kill bacteria than we were."

But the problem is that available antibiotics hit the same essential pathways. Over time bacteria has evolved to become resistant to antibiotics. This has led to a modern antibiotic crisis."

For instance, penicilin works well because it targets the cell wall, something humans don't have. So it kills the bacteria without hurting the patient. But it's easy for bacteria to resist.

RNA is different. It exists in all living cells, including those in people. Whitney said this toxin could kill people so it can't be used as an antibiotic but the pathway targeting RNA is something researchers can study.

When they first began researching the toxin and how it was killing bacteria, they were focused on how it affects protein because that's how other toxins typically target bacteria, Whitney said. This toxin is similarly structured to cholera and diphtheria.

But the test results were not successful. They tried DNA, but it too, was unsuccessful. So they finally tried RNA. He called trying RNA a kind of a hail Mary."

Whitney recalls it was a Sunday when the successful test results came in and his phone lit up with messages from Bullen in the lab.

It was exciting," he said.

They spent the next year studying how the toxin targets RNA. Whitney said there is still a lot more research that needs to happen, including understanding why at a molecular level the toxin targeting RNA is lethal.

Whitney and Bullen also worked with colleagues at Imperial College London and the University of Manitoba. Funding for the research came from Canadian Institutes for Health Research, Medical Research Council, National Science and Engineering Council of Canada and Canadian Light Source.

Nicole O'Reilly is a crime and justice reporter at The Spectator. noreilly@thespec.com