Bacteriophage barrage

Lytic life cycle. When a lytic bacteriophage attacks a cell (left), it injects its DNA and changes the bacterium into a virus-making machine. As the titer of the virus increases (right), bacteriophage enzymes punch holes in the cell wall, causing an explosion of viruses into the surrounding medium.

Although bacteriophages have been studied for decades as therapeutic agents, their use has not met with great success. The human immune system rapidly clears the viruses, and it mounts an adverse reaction upon repeated exposure. Harnessing the bacteriophages’ cell-bursting weaponry, however, is another story. Once the phage injects its nucleic acid into the bacterium, the cell becomes a virus-producing factory. For the lytic bacteriophages, once reproduction is complete, the newly formed viruses burst their way out of the cell using a specialized enzyme that attacks a cell wall component unique to the bacterial host.

Vincent Fischetti and his group at Rockefeller University (New York) reported the discovery of an enzyme that specifically targets group A streptococci—the cause of strep throat and flesh-eating disease (Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 4107–4112). In vitro, as little as 10 ng of the enzymes kills off millions of streptococci in seconds, and resistant bacteria have yet to be found despite extensive efforts to select for them. In mice, no adverse immune response was seen.

The enzymes would be used to eliminate the disease bacteria at their source, which in most cases is the human mucous membranes, according to Fischetti. “The organisms are generally spread from an infected or colonized individual through contaminated saliva. The enzyme could be given in the form of a spray, administered at frequent intervals—such as once or twice a day—to maximize effectiveness.”

The rapid-fire killing activity that these phages have evolved means that the emergence of resistant bacteria is less likely, he believes. “We’re taking advantage of the way nature selected for these events.”