Healthcare Infection Prevention-License to kill: Harnessed enzymes aimed at bacteria

But will breakthrough move from mice to men?

A novel approach to defeat streptococci species at the cellular level by introducing an ancient biological nemesis is nearing clinical trials in humans, researchers report.¹

While still under study with lab mice, the approach may lead to a throat spray or dissolving tablet that could rapidly eliminate carriage before it progresses to strep throat or pharyngitis. That could have major implications for preventing infections in day care, military camps, and other settings, researchers hope.

What is it? - A bacteriophage lytic enzyme that quickly destroys the cell walls of its target bacteria. After invading and replicating, the bacteriophage needs a way to quickly get out of host bacteria. The solution: a cell-wall eating enzyme.

Harnessing the enzyme

"[This is] a virus that infects bacteria," explains Vincent A. Fischetti, PhD, professor in the laboratory of bacterial pathogenesis at Rockefeller Uni-versity in New York City. "Basically, all bacteria have a bacteriophage system. We are just harnessing one of the enzymes that they produce during their exit from that organism. These enzymes have been developed by bacteriophages over eons."

It’s important to note that the researchers are not using the entire virus, but have found a way to remove the enzyme. "We are just purifying the enzyme in the final stages of the infection," he says. "It is not a virus. It is a protein specifically to cleave the cell walls of bacteria."

The enzyme has proved highly effective at killing groups A, C, and E streptococci. While it won’t cure existing infection, researchers estimate that between 30% and 50% of people carry group A streptococci asymptomatically.

"There is a reservoir for these organisms," Fischetti says. "So, in essence, if you treated children and adults on a regular basis with this enzyme, you would likely prevent infection by [eliminating] the organisms that they are transmitting from individual to individual."

The new weapon also could help preserve antibiotic efficacy by providing an alternative to prescribing drugs. "It’s not likely to cure an infection," he says. "You will still need antibiotics to do that. But certainly we can reduce the numbers of organisms, and we probably could use less antibiotics."

Since all bacteria have a bacteriophage complement, meaning the biological systems may eventually be used against other pathogens such as pneumococci and staphylococci, Fischetti says. If clinical trials proceed in humans, the first test group will likely involve military personnel, Fischetti says.

"Within four years I suspect we will have a [marketable] product," he says. "This is a platform technology. All pathogenic bacteria have a bacteriophage systems. If we can use this technology to develop enzymes for a wide range of pathogens, we can knock out the reservoir of these organisms - interrupting transmission to others and thus preventing infections."

Reference

1. Nelson D, Loomis L, Fischetti VA. Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme. Proc Natl Acad Sci 2001; 98:4,107-4,112.