Viral Enzyme Clears Ear Infection In Mice

MEMPHIS, Tenn., March 23 -- Clinicians may one day give children a weekly nasal spray of viral enzyme to prevent acute otitis media, researchers said here.

The notion is based on experiments in mice, in which the viral enzyme Cpl-1 lysin broke down the cell walls of Streptococcus pneumoniae and prevented the development of acute otitis media, according to Jonathan McCullers, M.D., of St. Jude Children's Hospital here.

The enzyme is derived from a bacteriophage, a virus whose target is bacteria, rather than animal cells, Dr. McCullers and colleagues reported in the open-access journal PLoS Pathogens.

While the heptavalent pneumococcal conjugate vaccine appears to be lowering the incidence of acute otitis media in the U.S., the disease remains the "leading reason for physician visits and antibiotic prescriptions among preschool-aged children," Dr. McCullers and colleagues said.

Much of the otitis media seen in the U.S. is caused by S. pneumoniae, because about half of all children are colonized with the bacteria. Viral infection allows the bacteria to ascend to the inner ear and trigger acute otitis media.

The researchers colonized mice with a strain of S. pneumoniae genetically engineered to express a luciferase enzyme, which causes the bacteria to emit light so that their presence or absence can easily be determined.

The mice developed acute otitis media in a manner analogous to human children, the researchers said. When the mice were infected with an influenza virus, the S. pneumoniae migrated to the inner ear and caused disease.

Indeed, of 30 bacteria-colonized mice infected with virus, 19 developed otitis media, compared with none of the bacteria-colonized mice given a mock infection with phosphate buffered saline. The difference was significant at P=0.00053.

In the crucial experiment, Dr. McCullers and colleagues said, bacteria-colonized mice were treated with Cpl-1 lysin or phosphate buffered saline before being infected with influenza.

They found:

• Nine of 10 animals treated with the enzyme cleared the bacteria within 24 hours, compared with none of the saline-treated mice, a difference that was significant at P=0.00012.
• None of the lysin-treated animals developed otitis media after influenza challenge, compared with 80% of saline-treated mice 80% -- a difference that was significant at P=0.00036.

None of the animals used in the experiments developed illness or toxicity attributable to the enzyme, the researchers said.

In a nasal spray form, the viral enzyme might eventually be used to prevent otitis media in humans, according to senior author Vincent Fischetti, Ph.D., of Rockefeller University in New York.

"The nasal spray may eventually be used weekly during the flu season to keep the person free of Streptococcus pneumoniae or after someone is infected with the flu virus," Dr. Fischetti said. "This might truly be a case in which an ounce of prevention would be worth a pound of cure."

The enzyme might also be useful during flu season and influenza pandemics, when much of the mortality is caused by secondary bacterial infections, Dr. McCullers said.

"Eliminating these secondary infections could dramatically reduce the sickness and death rates among susceptible populations such as infants and the elderly," he said.