Secret weapon of ‘flesh-eating bugs’ revealed
Bacteria hijack human protein to break through protective blood clots
Bacteria can use our own clot-busting system to spread around the body, according to US researchers. They hope their findings will be used to design drugs or vaccines to prevent certain types of infection becoming fatal.
Infections with group A Streptococcus (GAS) are common, and usually give people no more than a sore throat. But occasionally these bacteria manage to spread rapidly, and when they do, it can lead to death in more than a quarter of cases.
The body responds to GAS by building up blood clots around the infected area, corralling the bacteria. But the bacteria retaliate with an enzyme, called streptokinase, which causes the body to break down the clots, allowing the bacteria to escape and run rampant through the body. In such cases, patients may develop necrotizing fasciitis, the infamous 'flesh-eating' disease.
David Ginsburg and colleagues from the University of Michigan in Ann Arbor, have now worked out exactly how streptokinase does this. It activates a protein called plasminogen, which starts a chain reaction that makes blood clots more soluble. Inactive plasminogen is normally stored by the body until it is needed, but the bacterial streptokinase triggers the release of the clot-busting protein, washing away the barriers that keep the infection at bay. The research is published in this week's edition of Science1.
The team's discovery explains why the humble laboratory mouse is normally so resistant to GAS. Mouse plasminogen is different from the human form, and is not targeted by the streptokinase; GAS cause only localized infections when injected under the skin of a mouse, because its enzyme is not equipped to make blood clots break down.
To understand why, Ginsburg took genetically engineered mice that relied on human plasminogen for clot control, and injected them with GAS. The bacteria soon rampaged through the mice, killing most of them.
He then repeated the experiment, but used GAS that had had their streptokinase removed. This time, the mice suffered only localized infections, and none died. This pinpoints the interaction between streptokinase and human plasminogen as the root of the bacteria's spread.
Such knowledge could lead to a vaccine that blocks streptokinase and stops the bacteria spreading, says Ulf Sjöbring, a microbiologist from the University of Lund, Sweden, who was part of the research group.
"The data are very promising", says Staffan Normark, an expert on GAS infection at the Karolinska Institute in Stockholm, Sweden. "There is real excitement in the field about generation of these virulence inhibitors. This might be a breakthrough, but we'll have to wait and see," he adds.
Scientists suspect that other deadly bacterial infections spread in a similar way. The strain of 'super-bug' known as methicillin-resistant Staphylococcus aureus (MRSA), which causes such a serious problem in hospitals, also relies on an enzyme that activates plasminogen. So Ginsburg's discovery could help to tackle these kinds of infections as well, says Sjöbring
One mystery remains: why does GAS only cause serious problems in a few patients? Ginsburg thinks that this might be due to subtle differences between people's genes for plasminogen. Although this has not been confirmed, it might allow genetic testing to identify those most at risk of infection.
- Sun H., et al. Science, 305. 1283 - 1286 (2004).
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