Researchers solve flesh-eating bacteria's success
"flesh-eating" bacteria are so resistant to antibiotic treatment,
which could contribute to new strategies for treating necrotizing
fasciitis, halting its rapid destruction of tissue.
Necrotizing fasciitis is a serious but rare infection of the skin and the tissues beneath it. It is caused by the bacterium, group A Streptococcus and causes destruction on muscle and skin tissue, which kills approximately 30 per cent of its victims and leaves the rest disfigured.
Antibiotics and surgical interventions have a high failure rate due in part to a protein Streptococcus produces that blocks the immune system's distress calls.
Researchers from Hebrew University in Jerusalem have focused on SilCR - a gene for a Streptococcus peptide after finding that the gene product was turned off in a particular virulent strain of Streptococcus known as M14.
"This gene is supposed to produce a peptide that acts as a signalling molecule that the Streptococcus bacteria use to communicate with each other," said Emanuel Hanski, a microbiologist at Hebrew University in Jerusalem who is also a Howard Hughes Medical Institute (HHMI) international research scholar.
"Since the bacteria were not producing the peptide, we decided to synthesise it ourselves and give it to mice infected with M14."
The mice that received this peptide survived at a higher rate than mice that did not receive the peptide. The team also observed many white blood cells at the infection site in mice receiving the peptide.
The team then focused on interleukin-8, an important human immune system signalling molecule that is produced when the body senses infection to recruit white blood cells to the infection area.
The team discovered that the M14 strain of Streptococcus destroyed IL-8. But when the SilCR protein was added to the growing bacteria, the IL-8 survived.
"The amount of IL-8 that survives is inversely related to how much SilCR there is in the culture," said Hanski. "This may be one reason why some strains are less virulent than others; they might make more SilCR.".
The third part of the research aimed to establish a link between SilCR, a healthy immune response and IL-8 since the activity of all three still did not explain the underlying mechanism.
The team knew that SilCR itself did not degrade IL-8. Using advanced techniques to measure the levels of gene transcription products in a cell, they identified the enzyme ScpC.
To test their theory, the team created a mutant variation of the M14 strain of Streptococcus that would not produce ScpC.
Additional studies showed that this strain was less virulent than the original M14.
Only three of 28 mice receiving the mutant strain succumbed to infection and mice receiving the original bacteria developed lesions that grew until the mice died.
Mice receiving the mutant strain developed only small lesions that spontaneously healed.
"The experiments show that SilCR down-regulates the production of ScpC, and ScpC is what destroys the IL-8," said Hanski.
"In our strain, M14, SilCR is missing completely, which explains why it is so virulent."
The work points to more effective strategies for treating Streptococcus infection.
"You could look for a specific inhibitor of ScpC, or you could explore the activity of SilCR more fully and try to boost its action," said Hanski.
The findings are published in the October 4, 2006, issue of the EMBO Journal.
