Phage lysins as novel anti-bacterial agents ¬– Infection by drug-resistant bacterial human pathogens is a serious concern for healthcare in the U.S. Bacteriophages encode lysozyme-like enzymes called lysins that hydrolyze cell wall peptidoglycan and rapidly induce bacterial cell lysis. Because phage lysins bind to cell wall structures that are essential for cell viability (usually carbohydrates) bacteria do not develop resistance as easily as with traditional antibiotic drugs. In fact, lysin resistance, though tested extensively, has not been found with any of the currently identified lysins. Enzymes engineered for treatment of bacterial infections are part of a new class of antibiotics known as ‘enzybiotics’. A lysin encoded by gamma phage, PlyG, selectively kills Bacillus anthracis (the bacterial pathogen that causes anthrax) and can inactivate germinating spores in vivo to prevent anthrax infection.
A lysin encoded by gamma phage, PlyG, selectively kills Bacillus anthracis (the bacterial pathogen that causes anthrax) and can inactivate germinating spores in vivo to prevent anthrax infection. PlyG contains a conserved N-terminal catalytic domain similar to T7 lysozyme and a more divergent C-terminal domain that binds the cell-associated substrate and limits the range of suitable bacterial target species. We are currently solving the structure of PlyG in order to learn how its activity is selectively targeted to the cell wall of anthrax. Our collaborator Dr. Vincent Fischetti and his research group at Rockefeller University are searching for other phage enzymes with novel bactericidal activity that could be employed in the ongoing battle against antibiotic resistant bacteria that are now found throughout hospitals and communities across the U.S. We will work with them to define the structures of these potential enzybiotics and engineer them for clinical use. This work is funded as a research project of the Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (GLRCE)[LINK -- http://www.glrce.org]. Return to Dr. Volkman Home Page.
