NEW YORK CITY—Prophylactically eradicating Streptococcus pneumoniae from the nasopharyngeal mucosa with a specific bacteriophage hydrolase might limit the spread of infection among susceptible populations.[1] Pneumococcal bacteriophage lytic enzyme (Pal) has greater microbe specificity than antibiotics, and it may also work against strains vaccines exclude.

“We have now a substance that can be used to control colonizing disease organisms,” said Vincent A. Fischetti, PhD, Professor and Co-chairman of the Laboratory of Bacterial Pathogenesis at Rockefeller University. He and his colleagues had previously demonstrated selective action of the C1 bacteriophage enzyme lysin against group A streptococci.[2]

“There’s nothing currently available that will control the spread of streptococci found on the mucous membranes of the human oropharynx; prophylactic use of antibiotics is not indicated for this purpose due to potential resistance problems,” said Dr. Fischetti. And, he added, “the vaccines work quite well for the specific serotypes that are in the vaccines. But you can still be a carrier of that serotype, enabling spread to susceptible individuals.” Thus, there is a need for alternative methods of limiting streptococcal infection, which can cause otitis media, pneumonia, and even septicemia and meningitis among susceptible populations.

ENZYME KILLS IN VIVO, IN VITRO

In vitro, 100 U/mL of Pal killed 15 different serotypes of S pneumoniae, including three penicillin-resistant varieties, reducing viable titers approximately 10,000-fold within 30 seconds of application. Among mice intranasally colonized with S pneumoniae, Pal application 42 hours later yielded sterile nasal cultures five hours posttreatment. And, whereas streptococcal titers persisted in colonized mice treated only with buffer, nasal titers six days after Pal treatment were significantly lowered, suggesting that a single dose prevented successful recolonization.

Dr. Fischetti envisions using the enzyme as a nasal spray for prophylaxis among susceptible populations in nursing homes, hospitals, and day care. “Ideally, the best use of the enzyme would be to use it prior to infection. You would want to use it on a fairly regular basis—perhaps every five to seven days.” Being selective for S pneumoniae, Pal is unlikely to harm other nasopharyngeal microbes, and it has no apparent activity against mammalian cells. And, because it disrupts cell walls to kill microbes outright, “the enzyme is very efficient and acts quickly,” Dr. Fischetti noted to RESPIRATORY REVIEWS. Furthermore, he predicted, Pal is unlikely to trigger anti-enzyme antibodies, which could interfere with its activity. “The doses are very low—nanogram to sub-microgram amounts. That type of dose, with no mucosal adjuvant, is not very immunogenic on mucous membranes,” he explained.

Widespread use of the agent may be feasible, argued Dr. Fischetti. “It’s very inexpensive—pennies a dose to produce.” In addition, “it’s actually quite stable, with a half-life of over a week at 37ºC”; therefore, its action is limited mainly by its clearance from the oropharynx. To prolong activity, “we are trying to incorporate the enzyme into micelles that would adhere to mucous membranes,” he noted. Other microbes might be similarly targeted: Besides developing an enzyme specific for group A streptococci,[2] “we are working on one for staphylococcus, as well as some for other human pathogens,” said Dr. Fischetti.

—Mimi Zucker, PhD