



How does the staph superbug become so super?


Deb Anderson

A drug-resistant strain of golden staph

A drug-resistant strain of golden staph

GOLDEN staph is getting the better of every antibiotic science develops - with frightening speed. But University of Melbourne microbiologist Tim Stinear and infectious disease specialist Ben Howden, at Austin Health, have led a groundbreaking study to probe this hospital superbug. Dr Stinear says what they found, published this month in PLoS Pathogens journal, is staph needs only one subtle change to its DNA to develop resistance to last-line antibiotics.

What did you seek to learn?

Let's say you develop an infection with the bacterium Staphylococcus aureus, or golden staph - and it's the methicillin-resistant staph, the nasty one that's hard to treat with normal drugs. So the doctor puts you on the widely used last-line drug, vancomycin. In most cases that would clear your staph infection but in some patients it doesn't; 20 days later you can still be infected with staph in your bloodstream. We want to know why these people fail therapy with our last-line drug - and ''last line'' means last resort; we have very limited options after that. Does something happen to the bacteria in that patient?

What's your approach?

Austin Health is treating patients with these persistent bacterial infections; at the university we look in great detail at the bacteria. Our approach has been to take the isolates of staph from patients at the day they are diagnosed with an infection and then again 20 days later when they've failed therapy with vancomycin.

What do you do with those strains?

Using DNA sequencing, we sequence the complete genome of the bacterium for the first and last isolates. The power of genomics is that it shows us all the mutations that have developed in the bacterium over the course of that failed treatment. Modern DNA sequencing technology is akin to having a powerful torch to shine light on what was previously a very dark place.

What did you find?

We've found, for the first time, that you only need to change one tiny piece of the DNA - what we call a nucleotide, the minimum component of the DNA sequence of the microbe - and it's enough to allow the bug to reprogram itself, to make a slightly different cell wall, to do a few other different tricks that mean the antibiotic is not as effective any more. Worryingly, we also found this change also made staph more resistant to another last-line antibiotic, even though patients had never been treated with this agent.

That's incredible.

In one sense it is. But we shouldn't be surprised! DNA is the blueprint for all life and this is evolution in action. This is what living things do: we all respond to our changing environment.

So for medicine, it is an ongoing battle?

It is often referred to as an ''arms race'', and it's been going on for as long as we've been trying to defeat bacteria. When penicillin was introduced in the 1940s, resistance to penicillin appeared soon after. We modified penicillin, and then the bugs evolved resistance again. We've shown here, with a last-line drug, that the changes in DNA are subtler than we thought.

What was known before?

When bacteria develop resistance to an antibiotic, they acquire a whole gene or a set of genes. There are also examples of point mutations in bacteria causing antibiotic resistance but we've shown a new mechanism by which staph aureus can evolve resistance to vancomycin.

Your work suggests we need to improve the use of antibiotics. How?

That's the key question: knowledge is power but how are we going to use it? We could use vancomycin in a different way or change the dosage; or find a partner drug so the bacteria have to develop resistance to two drugs - a common strategy to fight other infectious diseases; or identify patients more at risk of developing these resistant infections and treat them differently.


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