How bacteria exploit proteins to trigger potentially lethal infections

May 2, 2014

New research by scientists at the University of York sheds light on how bacteria exploit human proteins during infections.

A research team led by Professor Jennifer Potts, a British Heart Foundation Senior Research Fellow in York's Department of Biology, studied how Staphylococcus aureus, which can cause life-threatening human infections, attach 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 infection infective endocarditis and the latest research suggest how the process occurs. The researchers, who included Vaclav Stemberk and Dr Richard Jones at York and Dr Ruth Massey, a microbiologist at the University of Bath, used X-ray crystallography, biophysical techniques and bacterial assays to investigate the process.

In research published in the Journal of Biological Chemistry, they solved the three dimensional structure of the bacterial protein FnBPA in complex with a small part of the human protein fibrinogen. This work showed that the fibrinogen binding site on FnBPA is close to, but not overlapping with, the binding site for fibronectin.

They then studied the binding of the two human proteins simultaneously to FnBPA and found that binding of fibronectin appears to block binding of fibrinogen to the bacterial protein. It appears that regulation of binding arises due to the close proximity of the fibrinogen and fibronectin binding sites on the 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.

Professor Potts said: "Bacteria have evolved various mechanisms to exploit human proteins to cause infection. Understanding these mechanisms might not only lead to the development of new therapeutics but can also provide important information regarding the normal role of these human proteins in the body."

Dr Sanjay Thakrar, Research Advisor at the British Heart Foundation, which co-funded the study, said: "The bacteria studied can cause a wide range of infections including the potentially fatal heart known as infective endocarditis.

"This study showed how this bacterium interacts with proteins found in our blood, which may give us an insight into how these deadly heart infections occur. This is an important step towards developing new treatments, but more research is needed to fully understand this interaction."

Explore further: New step forward in search for solution to infection puzzle

More information: The paper 'Evidence for Steric Regulation of Fibrinogen Binding to Staphylococcus aureus Fibronectin-binding Protein A (FnBPA)' is published in the Journal of Biological Chemistry.

Related Stories

New step forward in search for solution to infection puzzle

August 6, 2008

Scientists at the University of York have helped to reveal more about the way bacteria can attach to human tissues. The study could help in the development of new treatments for serious heart conditions such as infective ...

A novel target for therapeutics against Staph infection

November 28, 2008

Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology, and the University of Edinburgh have uncovered how a bacterial pathogen interacts with the blood coagulation protein fibrinogen to ...

Recommended for you

Atom-sized craters make a catalyst much more active

November 24, 2015

Bombarding and stretching an important industrial catalyst opens up tiny holes on its surface where atoms can attach and react, greatly increasing its activity as a promoter of chemical reactions, according to a study by ...

Getting under the skin of a medieval mystery

November 23, 2015

A simple PVC eraser has helped an international team of scientists led by bioarchaeologists at the University of York to resolve the mystery surrounding the tissue-thin parchment used by medieval scribes to produce the first ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.