"Molecular lasso" helps bacteria catch-and-clamp onto your heart
Bacteria can be crafty little critters, and a new study from the University of Bristol has unveiled another example of that. Usually a harmless resident of your mouth, Streptococcus gordonii can turn lethal if it enters your bloodstream, where the researchers discovered it uses a "molecular lasso" to attach itself to host cells in what they call a catch-clamp mechanism. Understanding the process could lead to new treatments of a serious condition known as infective endocarditis.
This form of cardiovascular disease is caused by bacteria like S. gordonii creating blood clots on the heart valves, and it's fatal in as many as 30 percent of cases. While the new finding isn't exactly a new treatment, it could be the first step toward one.
"What our work has revealed is a completely new mechanism by which S. gordonii and related bacteria are able to bind to human tissues," says Catherine Back, lead author of the study. "We have named this the 'catch-clamp' mechanism."
The University of Bristol team first zeroed in on a protein called CshA. Previous research suggested that S. gordonii uses this protein to latch onto human cells, but exactly how it does so was unclear.
Using an X-ray microscope, the researchers observed the bacteria whipping CshA out like a molecular lasso, and grabbing hold of a glycoprotein on the surface of the human cells called fibronectin. That's the "catch" part of the equation. The "clamp" part comes next, as the bacteria uses the anchor to drag itself toward the host cells, before using another section of the CshA protein to clamp down and settle in.
Antibiotics can kill off the invaders, but as the specter of antibiotic-resistant "superbugs" looms large, this might not be an effective treatment long-term. Clever as the catch-clamp mechanism is, it actually offers two potential points of failure that scientists could exploit for future treatment options.
"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," says Paul Race, co-researcher on the study. "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."
The researchers' next step may be to begin investigating anti-adhesive agents that can target S. gordonii and other bacteria that use a similar system.
The research was published in the Journal of Biological Chemistry.
Source: University of Bristol