A Lego-Like Approach to Improve Nature’s Own Ability to Kill Dangerous Bacteria
Research capitalizes on ability of enzymes to target and kill bacteria, improving possible solution to problem of antibiotic resistance
The Centers for Disease Control and Prevention consider antibiotic resistance to be one of the most urgent public health threats, a threat that affects communities around the world. In their search for solutions against this resistance, researchers at Rensselaer Polytechnic Institute have turned to nature.
Using nature to fight bacteria
The team demonstrated how it could improve the ability to selectively collect naturally occurring antimicrobial enzymes to attack bacteria in a way that is much less likely to cause bacterial resistance.
"The idea is that we could take the approach to nature and simply improve it," said Jonathan Dordick, professor of chemical and biological engineering who led this research with Domyoung Kim, postdoctoral researcher and Seok-Joon Kwon, senior scientist. For bacteria to grow and live, they naturally produce autolysin enzymes that can break down their own cell walls, allowing these cells to divide and multiply.
By attacking each other, bacteria take advantage of a similar process, using an antibacterial protein known as bacteriocin to kill a bacterium. Bacteria can also be attacked by bacteriophages. They produce phage endolysin enzymes, which attack the bacterial cell from the inside. These three types of enzymes are known as cellular lytic enzymes because they catalyse the degradation of the bacterial cell wall.
Cellular lytic enzymes are modular
"It is very difficult for bacteria to become resistant to the action of these enzymes," says Dordick, "For example, if they became resistant to an autolysin, they would no longer divide. "Like building blocks, most cellular lytic enzymes are modular. They consist of a binding domain that binds to the cell wall and a catalytic domain that breaks holes in the cell wall and effectively destroys targeted bacteria.
In this article, scientists explored whether they could improve these combinations that nature has created. "The idea was: could we use an approach similar to that of these building blocks? Can we take a binding domain of one enzyme and mix it with a binding domain or a catalytic domain of another? "Dordick said.
More specifically, the team took streptavidin, a protein that acts as an effective model to which researchers could attach a binding domain of one organism and a catalytic domain of another. This modular approach allows them to quickly make new combinations to determine which ones will work best.
The combination of researchers was better than what nature can do
They found that by targeting Staphylococcus aureus - commonly known as staphylococcus aureus - their combinations were very effective, sometimes even better than what nature can do. "We have genetically expressed the binding or catalytic domains of several different organisms," said Mr. Dordick, "We have identified some that work better than what nature can provide. This paves the way for a whole new way of developing antimicrobial enzyme systems. »
"This research has the potential to improve human health," said Deepak Vashishth, Director of CBIS, a research centre that brings together professors from many disciplines to solve these complex problems. "It is emblematic of the innovative solutions needed to advance medical care against resistance. »
Results that lay the foundation for future research
These results provide the basis for further research to control and redesign various microbiomes found in nature and, eventually, to be used in clinics, for example, to control skin and intestinal infections.
