Phage Lysins
Our lab is using phage lysins as a novel method to control infection. Phages are viruses that specifically infect bacteria. After replication inside its bacterial host the phage is faced with a problem, it needs to exit the bacterium to disseminate its progeny phage. To solve this, double-stranded DNA phages have evolved a lytic system to weaken the bacterial cell wall resulting in bacterial lysis and phage release. Phage lysins are highly efficient molecules that have been refined over millions of years for this very purpose. These enzymes target the integrity of the cell wall, and are designed to attack one of the five major bonds in the peptidoglycan. With few exceptions, lysins do not have signal sequences, so they are not translocated through the cytoplasmic membrane to attack their substrate in the peptidoglycan; this movement is controlled by a second phage gene product in the lytic system, the holin. Scientists have been aware of the lytic activity of phage for nearly a century, and while whole phages have been used to control infection (phage therapy), our lab was the first to exploit phage lysins for bacterial control in vivo. Current data indicate that lysins work only with gram-positive bacteria, since they are able to make direct contact with the cell wall carbohydrates and peptidoglycan when added externally, whereas the outer membrane of gram-negative bacteria prevents this interaction. We have now developed lysins that control a wide range of gram-positive pathogens such as S. pyogenes, S. aureus, S. pneumoniae, E. fecalis, E. faecium, B. anthracis, and group B streptococci.
Phage Lytic Enzymes Currently Developed in the Fischetti Lab
