A new enzyme identified by University of Maryland researchers has unique capabilities to combat life-threatening infections caused by Staphylococcus bacteria.
Associate Professor Dr. Daniel C. Nelson of the Department of Veterinary Medicine and the Institute for Biosciences and Biotechnology Research along with his team have discovered an enzyme that selectively targets the Staphylococcus bacteria and ruptures the bacteria cell wall, rendering the bacteria inactive. This new innovation is one of nine nominees for Invention of the Year Award.
The enzyme, PlyGRCS, is an endolysin enzyme that is actually produced by a bacteriophage (a virus that lives and multiplies inside bacteria) that cleaves the cell wall of Staphylococcus, Nelson said.
“Significantly, when we purify this enzyme and drop it on Staphylococcus aureus cells, the enzyme rapidly hydrolyzes and chews up the cell wall, which results in the death of the bacterium,” he said.
Nelson called this a novel approach and an alternative to traditional antibiotics.
“Since the enzyme utilizes a mechanism that is completely different from all known antibiotics, it works against all antibiotic-resistant Staphylococcus aureus, such as methicillin-resistant Staphylococcus aureus (MRSA) as well as vancomycin-resistant Staphylococcus aureus (VRSA),” he said.
Nelson explained that while there are many endolysins that can chew up the cell walls of MRSA effectively, the new enzyme can simultaneously cleave it in two places.
“PlyGRCS cleaves the same web in two dimensions, which is far more destabilizing, and ultimately leads to higher lytic (killing) activity for our enzyme compared to other known staphylococcal endolysins,” he said.
Nelson and his research group have successfully cultured this enzyme in bacterial cells.
“We took the gene for PlyGRCS, optimized the codon usage specific for expression in E. coli, and had the new gene artificially synthesized by a company. Obviously, for commercial use, large scale fermentation systems would be used which would further optimized the yield,” Nelson said.
“One may envision impregnating PlyGRCS in a bandage or wrap for these applications,” he said.
Other potential applications include using it against biofilm infections caused by staphylococci and treating bovine mastitis.
“We are applying for funds from the USDA to conduct therapeutic evaluation of PlyGRCS for bovine mastitis indications,” he said. Bovine mastitis in dairy cows is a significant problem, responsible for a $2 billion economic loss every year in the U.S. alone.
Nelson is currently working on evaluating the in vivo efficacy of PlyGRCS in animal models. In fact, this resulted from Nelson’s contact with the Office of Technology Commercialization (OTC).
“The OTC staff also relayed to me that they were contacted by a biotechnology company interested in PlyGRCS, but their interest would have been stronger if we had animal studies showing efficacy. This information helped shape our continued research on this enzyme,” he said.
Follow-up plans also include studying the anti-biofilm properties of this enzyme in central line catheter flow cells, for additional clinical application of the enzyme. Additionally, in order to improve the enzyme’s properties, bioengineering studies will be conducted to swap the enzyme’s binding domain with those of other staphylococcal endolysins.
“This would represent the ‘next generation’ of endolysins,” Nelson said.
Nelson’s work is a nominee for the University of Maryland Invention of the Year Awards, which will be announced on April 29, 2015. For more information, visit research.umd.edu or techtransfer.umd.edu.
April 14, 2015