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The human mouth can harbour more than 700 different species of bacteria, which usually co-exist with us as part of our oral microbiota. (Image: Maxx-Studio/Shutterstock)
0 Comments Feb 24, 2017 | News UK & Ireland

New research targets disease-causing oral bacteria

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BRISTOL, UK: When oral bacteria spread to other tissues via the bloodstream, the results can be catastrophic. Researchers have now discovered a potentially key molecular process that occurs in the case of infective endocarditis. The findings could lead to the development of new drugs to help combat this life-threatening heart disease.

Infective endocarditis is a type of cardiovascular disease in which bacteria cause blood clots to form on heart valves. If untreated, this condition is fatal and, at up to 30 per cent, the mortality rate remains high even with treatment. There are over 2,000 cases of infective endocarditis in the UK annually and the incidence is rising.

A key part of a study conducted at the University of Bristol involved use of the UK national synchrotron facility, Diamond Light Source. By means of this giant X-ray microscope, the team were able to visualise the structure and dynamics of a protein called CshA, which previous studies at the university had suggested played an important role in targeting the oral bacterium Streptococcus gordonii at the tissues of the heart. The researchers were intrigued to find that CshA acts as a molecular lasso to enable S. gordonii to bind to the surface of human cells. Such adhesive interactions are critical first steps in the ability of this bacterium to cause disease.

Lead author Dr Catherine Back, postdoctoral research associate at Bristol’s School of Oral and Dental Sciences, said: “What our work has revealed is a completely new mechanism by which S. gordonii and related bacteria are able to bind to human tissues. We have named this the ‘catch-clamp’ mechanism.”

The team were able to demonstrate that the terminal portion of CshA is very flexible. This allows it to be cast out from the surface of the bacterium like a lasso. When the lasso contacts fibronectin on the surface of human cells (the catch), it brings CshA and fibronectin into close proximity. This then enables another portion of CshA to tightly clamp the two proteins together, anchoring S. gordonii to the host cell surface.

Co-researcher Dr Paul Race, senior lecturer at the university’s School of Biochemistry and the BrisSynBio research centre, said: “What is particularly exciting about this work is that it opens up new possibilities for designing molecules that inhibit either the ‘catch’ or the ‘clamp’ steps in this process, or potentially both. The latter possibility is particularly intriguing, as bacteria are generally less likely to become resistant to agents that target multiple steps in an infective process.”

Dr Angela Nobbs, lecturer at the university’s School of Oral and Dental Sciences, also co-author of the study, added: “With the molecular level insight that our study provides, it is now a realistic possibility that we can begin to develop anti-adhesive agents that target disease-causing Streptococcus and related bacteria.”

The study, titled “The Streptococcus gordonii adhesin CshA binds host fibronectin via a catch-clamp mechanism”, was published online on 5 December 2016 in the Journal of Biological Chemistry.

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