Dozens of test tubes in a holder

Pivotal step forward in understanding an important enzyme that is encoded by bacterial viruses

Tue, Jul 24, 2012

Research from the laboratory of Dr. Daniel Nelson (UM IBBR/VETMED) and colleagues have made a pivotal step forward in understanding an important enzyme that is encoded by bacterial viruses (bacteriophage). The multidisciplinary group, that includes researchers from the University of Maryland, the National Institute of Standards and Technology, and The Rockefeller University, and Monash University in Australia, worked together to determine the structure and mechanism of action, including cell wall binding and catalytic activity of the streptococcal C1 phage lysin, PlyC. These findings, titled “X-ray crystal structure of PlyC, a novel enzybiotic”, were recently published in the journal The Proceedings of the National Academies of Science (PNAS). PNAS is well known to be one of the world’s most cited scientific journals that publishes original research.

The published research focuses on the structural analysis of the PlyC lysin of the streptococcal C1 phage. Lysins, such as PlyC, are encoded by bacteriophage as part exit strategy from the bacterial host. PlyC is the most potent lysin described to date and while the enzymatic activity has been extensively studied, the structure and mechanism of action have not elucidated. Using sophisticated labeling and molecular biology techniques, the investigators were able to crystallize the PlyC holoenzyme, including the two components that comprise it (PlyCA and PlyCB). The structural data revealed several interesting features of the enzyme, including that PlyCA contains two catalytic domains.  The eight cell wall binding domains together with these two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme on target bacteria. This research is a significant advance toward defining the molecular mechanisms of multi-subunit bacteriophage lysins.

The research Dr. Nelson’s laboratory at UM-IBBR includes studies on several proteins derived from bacterial viruses, or bacteriophage, that possess an inherent antimicrobial potential against both human and animal pathogens. The interests bring an innovative approach to identifying novel tools for the diagnosis and treatment of pathogenic bacterial infections.