NEW YORK CITY—Researchers at The Rockefeller University in New York City have developed a promising new technique for destroying bacteria that could lead to an alternative to antibiotics. The therapeutic equivalent of a “smart bomb,” the technique uses an enzyme that kills harmful bacteria on contact while preserving helpful organisms.

The enzyme is produced by bacteriophages—tiny viruses that infect a bacterium and replicate inside it. “The bacteriophage then has to escape the bacterium and release its progeny,” said Vincent A. Fischetti, PhD, the study’s lead investigator, in an interview with RESPIRATORY REVIEWS. “To do so, it produces an enzyme that degrades the bacterial cell wall. By purifying the enzyme, we’ve just harnessed that power.”

SETTING THE RESEARCH CROSSHAIRS FOR GROUP A STREP

The investigators’ current target is group A streptococci, which cause more than 2.5 million cases of pharyngitis in the United States annually. Although group A streptococci can cause severe disease, they are surprisingly easy to destroy, said Dr. Fischetti, cohead of the Laboratory of Bacterial Pathogenesis at The Rockefeller University. “We can take 10 million organisms in a test tube, add a very small amount of enzyme, and within five seconds, they’re all dead.”

But it is prophylaxis, rather than cure, that holds the most potential. “Our goal is to use these enzymes to eliminate the carriage of disease organisms,” explained Dr. Fischetti. “For instance, up to 30% of the population carry group A streptococci asymptomatically in their oropharynx. … [F]or the first time, we have a way to eradicate these organisms, without using antibiotics.”

ON THE ROAD TO CLINICAL TRIALS

The enzyme being studied by Dr. Fischetti and his colleagues is a lysin released by C1 bacteriophages, which specifically infect group C streptococci. The lysin can destroy groups A and E streptococci as well. Thus far, the enzyme has been tested in mice with excellent results. In addition to successfully protecting against infection, the enzyme has also wiped out the organism in mice that were heavily colonized with group A streptococci. Human studies might begin soon.

The problem of antibiotic resistance was the major impetus for this research. And streptococci are just the beginning; the Rockefeller team is currently purifying antipneumococcal and antistaphylococcal enzymes as well. “Those are the three major upper respiratory pathogens that can be controlled easily with this technology,” Dr. Fischetti observed. “The enzymes could be used in day care centers, hospitals, and nursing homes, for example, where these organisms are carried and are the reservoir for subsequent infections. Eliminating the source will greatly impact disease.”

The specificity of the enzymes renders them extremely safe. Although they are lethal for group A streptococci (and other targeted bacteria) residing on mucosal epithelium, they do not harm indigenous microflora. How soon might we see these enzymes in the clinical setting? “Because of their targeted nature, I think we might move along fairly quickly,” said Dr. Fischetti. “I suspect we might have a product in four or five years.”

—Nina Tobier