Using the power of nature against bacteria
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. Branches of the ability of bacteria to become resistant to antibiotics can be seen in hospitals, public places, our food supply and our water.
In their search for solutions, researchers at Rensselaer Polytechnic Institute have turned to nature. In a recent article published in Biomacromolecules, the team demonstrated how it could improve the ability of the selective collection of antimicrobial enzymes from nature to attack bacteria in a way that is much less likely to cause bacterial resistance.
"The idea is that we could take the approach of nature and simply improve it," said Jonathan Dordick, Professor of Chemical and Biological Engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research in Rensselaer 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, which are viruses that infect bacteria. They produce phage endolysin enzymes, which attack the bacterial cell from the inside. All three types of enzymes are widely known as cellular lytic enzymes because they catalyse the degradation of the bacterial cell wall.
"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 not 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.
These enzymes are very specific, Dordick said, targeting one or only a few bacteria. In this article, the researchers investigated whether they could improve the combinations that nature has created.
"The idea was: Could we use an approach similar to that of Lego? 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. The modular approach allows them to quickly make new combinations to determine which ones work best.
They found that by targeting Staphylococcus aureus - commonly referred to as staphylococcus aureus - their combinations were very effective, sometimes even better than in nature.
"We genetically expressed the binding or catalytic domains of several different organisms," said Mr. Dordick, "We identified some that worked better than what nature provided us. 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 complex problems. "It is emblematic of the innovative solutions needed to advance medical care."
These results provide the basis for further research and improved team creation of paints or coatings that could be applied to surfaces to search for and kill targeted bacteria, control and remediate various microbiomes in nature and potentially be used in clinics, for example, to control skin and intestinal infections.
This work was carried out in collaboration with a group led by Jungbae Kim, Professor of Chemical and Biological Engineering at Korea University. He received a grant from the Global Research Laboratory Program through the National Research Foundation of Korea.
