Each year, around 15 million children fall ill with rheumatic heart disease worldwide; half a million of them die as a consequence. At the beginning of the medical cases of these children stands a simple throat infection with streptococcus – spherical bacteria responsible for causing a range of different infections. However, it is only certain streptococcal strains that trigger a whole chain of reactions in the body that culminates in the life-threatening rheumatic heart disease. These bacteria carry a special protein sequence, the so-called PARF motif, on their surface.
Singh Chhatwal and his colleague Patric Nitsche-Schmitz of the Helmholtz Centre for Infection Research (HZI) in Braunschweig illustrate the role played by PARF in the development of rheumatic heart disease. With this knowledge they are developing a test system that is able to recognise and prevent the disease at an early stage.
"PARF means 'peptide associated with rheumatic fever'," explains Nitsche-Schmitz. "It is a small section from a bacterial surface protein , which is used by the streptococcus to adhere to our cells and cause disease." Rheumatic fever develops from harmless sore throats amongst children in India, Australia and Africa in particular. The reason: inadequate medical treatment.
If children with a streptococcus infection in the throat receive no or inadequate antibiotic treatment, then the surviving bacteria with the PARF sequence on their surface will adhere to their collagen. Collagen is present throughout the body – as a major component of bone and cartillage it determines shape and structure of our body and it strengthens the connective tissue of the skin, the heart valves and blood vessels with its high resistance to tensile forces. Adhesion of PARF-bearing streptococci to collagen confuses our immune system and our body's defence system not only targets the bacteria, but also healthy and vital collagen. The auto-immune disease rheumatic fever breaks out. If this in turn also fails to be treated correctly, the consequence is rheumatic heart disease: the heart valves, rich in collagen, become inflamed and cease to function.
Overall, only around five percent of all throat infections with streptococci result in an auto-immune disease. In order to filter out these five percent and treat them at an early stage, the Braunschweig infection researchers are developing a simple test strip that reacts to the PARF motif. "We hope that this will soon give us a test system that we can use for examination of children on a routine basis," says Singh Chhatwal: "This would save the lives of a lot of children."
- Dinkla et al. Crucial Role of the CB3-Region of Collagen IV in PARF-Induced Acute Rheumatic Fever. PLoS ONE, 2009; 4 (3): e4666 DOI: 10.1371/journal.pone.0004666
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