FEB 08, 2017 9:22 AM PST

Molecular "Catch-Clamp" Mechanism Explains Infective Endocarditis

WRITTEN BY: Kara Marker

A giant x-ray microscope from the UK national synchrotron facility revealed the structure and dynamics of a protein called CshA, which is apparently involved in the progression of infective endocarditis. This is a potentially fatal bacterial disease that occurs when bacteria invade the bloodstream.

An endocarditis ultrasound; vegetation on tricuspid valve by echocardiography. Source: Boundless

The human mouth can handle a lot of bacteria, acting as a reservoir for healthy microbes that live peacefully in the mouth. But outside the mouth, the same bacterial species that co-exist harmlessly can cause dangerous diseases in the body, like endocarditis.

A new study from University of Bristol scientists was prompted by previous research that identified CshA as responsible for binding the bacterium Streptococcus gordonii to the surface of human heart cells. Researchers describe the interaction as a “molecular lasso.”

"What our work has revealed is a completely new mechanism by which S. gordonii and related bacteria are able to bind to human tissues,” explained lead author Dr. Catherine Back. “We have named this the 'catch-clamp' mechanism." University of Bristol researchers estimate that there are over two thousand cases and growing of infective endocarditis in the UK annually.

The mechanism works like this. The particularly flexible terminal end of CshA acts as the lasso, connecting CshA with a protein called fibronectin, a component of the extracellular matrix (ECM). This is a structural network that enables cells to connect with one another. Another portion of CshA then binds to fibronectin tightly, successfully anchoring S. gordonii to the host cell surface.

"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,” explained co-researcher Dr. Paul Race. “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."

When bacteria from the mouth enter the bloodstream and cause infective endocarditis, they can travel to the lining of the heart and cause unwanted blood clots to form on heart valves. Without treatment, endocarditis is fatal, but even with treatment the disease has a relatively high mortality rate.

"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,” said study co-leader Dr. Angela Nobbs.

The present study was published in the Journal of Biological Chemistry.

Sources: American Heart Association, Theoretical and Computational Biophysics Group, University of Bristol

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
SEP 18, 2019
Cardiology
SEP 18, 2019
Clear, Flexible Vital Sign Wearable Monitors
Wearable health monitors are gaining in popularity, both for fitness tracking and for gathering more targeted health data relating to heart disease and oth...
OCT 09, 2019
Drug Discovery & Development
OCT 09, 2019
Drug Increases Survival Rates for Heart Failure Patients
Scientists have demonstrated in preclinical studies that a drug called ‘Aliskiren’ works by inhibiting the activity of an enzyme involved in bl...
DEC 01, 2019
Plants & Animals
DEC 01, 2019
Blue Whales Exhibit 'Extremely Low' Heart Rates When Performing Deep Dives
Blue whales have a reputation for being massive, and as far as we know, they’re the largest living animal in existence today. Perhaps unsurprisingly,...
FEB 21, 2020
Cardiology
FEB 21, 2020
Poor Sleep Increases Heart Disease Risk in Women
Researchers from Columbia University Irving Medical Center have found that women who don’t sleep well leading tend to have a lower quality diet and t...
FEB 20, 2020
Cardiology
FEB 20, 2020
Most Commonly Birth Defects Affect The Heart
Birth defects are not uncommon. For every 33 babies born in the United States each year, one is born with a defect. That adds up to about 120,000 babies ea...
MAR 08, 2020
Cardiology
MAR 08, 2020
Cashier and Healthcare Jobs Increase Risk of Heart Problems in Women
Stress has long been known to be a major risk factor for developing heart disease. Now, researchers from Drexel University in Philadelphia have found that ...
Loading Comments...