New research by scientists at the University of York, published in the Journal of Biological Chemistry, sheds light on how bacteria exploit human proteins during infections. Researchers studied how Staphylococcus aureus, which can cause life-threatening human infections, attaches to two proteins, fibronectin and fibrinogen, found in human blood.
The human proteins play important roles in clot formation and wound healing, and the bacteria appear to exploit them during the process of infection. Scientists had earlier shown that the binding sites for fibrinogen and fibronectin on the S. Aureus protein FnBPA appear to “co-operate” in causing the dangerous heart infection infective endocarditis, and the latest research suggests how the process occurs. The researchers used X-ray crystallography, biophysical techniques, and bacterial assays to investigate the process.
The researchers solved the three dimensional structure of the bacterial protein FnBPA in complex with a small part of the human protein fibrinogen. Their work showed that the fibrinogen binding site on FnBPA is close to, but not overlapping with, the binding site for fibronectin. They also discovered that regulation of binding arises due to the close proximity of the fibrinogen and fibronectin binding sites on the bacterial protein and the large size of the human proteins. While the research provides the first biophysical evidence in support of the co-operation previously observed in the infection studies, it is still not clear how these two observations are linked. The scientists are planning further studies.
Dr Sanjay Thakrar, Research Advisor at the British Heart Foundation, which co-funded the study, says, “The bacteria studied can cause a wide range of infections including the potentially fatal heart infection known as infective endocarditis. This is an important step towards developing new treatments.” Read the study.
Read more
