DNA detectives unravel superbug's secrets

24 May 2007

For the first time ever, scientists have tracked the step-by-step genetic changes that help superbug MRSA resist doctors' most powerful antibiotics. Experts hope that exposing exactly how the bug evolves its drug-defying abilities will give us new ways to fight the infection.

Antenna investigates...

Image: Krzysztof Sieradzki

If MRSA gets into the blood, it can cause real problems - the bacteria above have attacked red blood cells, breaking them down into 'halos' of debris.

Image: Krzysztof Sieradzki

We share our bodies with up to 10,000 different species of bacteria, most of which do us no harm. But it's an uneasy truce. When our immune defences are down, some of these bacteria turn nasty - such as Staphylococcus aureus, the bug behind MRSA.
MRSA infections can be deadly because the bug has evolved resistance to a whole group of antibiotics. This group, called the 'beta lactams', includes penicillin.
To make matters worse, the bacteria is starting to win the war against newer drugs too. Now experts have tracked an MRSA infection over time in a single patient to work out how the bug becomes so tricky to treat.

MRSA stands for methicillin-resistant Staphylococcus aureus.

Image: Krzysztof Sieradzki

How to track a superbug...
'The patient had an MRSA infection involving one of his heart valves,' explains lead researcher Alexander Tomasz, from the Rockefeller University in New York. 'He was treated with several antibiotics, and samples of his blood were taken over three months.'

Staphylococcus aureus with intermediate levels of resistance to vancomycin.

Image: CDC/ Matthew J. Arduino, DRPH; Janice Carr

During this time the MRSA became resistant to most of the antibiotics, including vancomycin - one of the few treatments that still work against MRSA.
Alexander and his team used samples of the superbug from the patient's blood to read its entire genetic code - its 'genome'. This meant they were able to track the precise mutations in its DNA that gave it resistance to antibiotics. No-one has studied an MRSA infection in this much detail before.
'Over three months, there were mutations in around 30 genes in the MRSA genome,' explains researcher Mike Mwangi, from the Rockefeller University. 'These mutations helped the bacteria fight off powerful antibiotics, including vancomycin. They also made it resistant to a new antibiotic that hadn't even been given to the patient.'

The bacteria were all descended from a single MRSA cell, which meant scientists could track changes in their DNA.

The patient had billions of MRSA bugs growing inside his body, and despite doctors' best efforts, he eventually died. But Alexander and Mike hope the samples of MRSA that he provided could help others fight off the superbug.
'Part of the problem of identifying how MRSA becomes resistant to antibiotics is working out what changes occur in its DNA,' says Mike. 'There are 3000 genes in the MRSA genome, and a mutation could happen anywhere. Now we know where to look.'

Mike Mwangi, MRSA expert, Rockefeller University.

Image: Mike Mwangi

Other experts are impressed with the research. 'It's showing us something we've never seen before,' says superbug expert Mark Enright, from Imperial College London. 'It could help us engineer changes to current antibiotics and make new drugs to fight MRSA.
'This study also shows how powerful genome-reading technology has become. In 10 to 20 years we should be able to read a genome so quickly that doctors can use it to diagnose a patient at their bedside.'

Mark Enright, MRSA expert, Imperial College London.

Image: Mark Enright

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