For years, clinicians and scientists have known that many frontline antibiotics are becoming less reliable. Bacteria constantly evolve, and many have found ways to evade the effects of antimicrobial drugs. These evasive methods, which are often encoded in genes, can easily be shared with other bacteria, and drug-resistant germs are becoming more common, more dangerous, and harder to destroy. In a new study reported in mBio, researchers analyzed how a common infectious microbe links to a host cell that it aims to infect. Learning more about this process could lead to ways to stop infections before they even start, rather than waiting to kill infected cells after they harbor pathogens.
"We're really interested in finding out how bacteria make their connection with the host cells they're going to infect," said corresponding study author Dr. Peter Davies, professor at Queen's University.
In this work, researchers used sophisticated techniques to visualize the structure of bacterial proteins known as adhesins. Most bacteria produce some adhesins, and these long, thin proteins can bind to sugar molecuels on the surfaces of other cells that could be infected.
After an adhesin binds to something, it can start forming a biofilm. These colonies of bacteria can be extremely hard to remove, as biofilms often take on new, complex properties that make them much tougher than individual bacterial cells.
The investigators used computational tools to generate a three-dimensional adhesin protein model, and analyze how they stick to other cells. One particular part of the adhesin they analyzed links up with a simple sugar molecule often found on human blood cells, called fucose.
Next, the scientists searched for ways to interfere with the binding process between adhesin and fucose. They determined that when the cells were exposed to lots of fucose, the bending was disrupted since so much fucose was available; the bacteria began to bind to any random fucose molecules instead of those on other cells.
Now, the researchers want to find drugs that could stand in for fucose, but could not be metabolized by bacterial or human cells. "We won't have to put so much sugar in the system," explained Davies. "We're thinking about how we can make this into a drug that will replace antibiotics to some extent."
This method aims to stop infections before they even start, but more work will be needed before we have a drug that people can take to prevent bacterial infections. It is a promising new avenue of research, however, in an area where we need more innovation.
Sources: Canadian Light Source, mBio