http://www.stjude.org/search/0,2616,582_3161_22746,00.html

Viral enzyme recruited in fight against ear infection
MEMPHIS, Tenn. - March 22, 2007
Parents might one day give their children a weekly treatment with a
nasal spray of virus enzymes to prevent them from getting a severe
middle ear infection, based on results of a study done in mice by
investigators from St. Jude Children's Research Hospital and The
Rockefeller University in New York. Such a treatment would kill the
disease-causing bacteria without the use of antibiotics, thereby
avoiding the problem of antibiotic resistance. A report on this study
appears in the March issue of the online journal PLoS Pathogens.

Middle ear infection, also called acute otitis media, is an
inflammation of the middle ear space that can cause pain, fever,
irritability, lack of appetite and vomiting. The middle ear is the
space just before the eardrum. About half of all children carry the
bacteria that cause acute otitis media, which migrate from the nose
and throat to the middle ear after an initial influenza virus
infection paves the way.

The investigators based their treatment on the ability of viruses
called phages to break out of bacteria they infect by using a special
enzyme to destroy the cell walls. Phages infect bacteria in a way that
is similar to how viruses infect animal cells. Once inside, the virus
hijacks the cell's biochemical machinery and forces it to make many
copies of the virus. After the new crop of viruses is made, a viral
enzyme breaks apart the infected bacterial cell wall and allows the
new viruses to escape and infect additional cells.

The success of the new treatment, which uses a phage enzyme to kill
the bacteria that cause acute otitis media, suggests that the strategy
could significantly reduce the incidence of the disease in the United
States, where more than 24 million cases are diagnosed yearly. Even
though the current pneumonia vaccine protects against Streptococcus
pneumoniae-the bacteria that cause acute otitis media-this ear
infection remains the leading cause of doctor visits and antibiotic
prescriptions among preschool-aged children. In the current study, the
researchers treated mice with the enzyme lysine, the same enzyme used
by phages to break out of S. pneumoniae.

In addition to its promise for preventing acute otitis media, the
virus enzyme treatment also appears to hold promise for preventing the
secondary pneumonia caused when a person infected with S. pneumoniae
is subsequently infected with the influenza virus.

"Secondary bacterial infections cause much of the sickness and about
25 percent of all deaths during the flu season, and 50 to 95 percent
of deaths during pandemics of influenza," said Jonathan McCullers,
M.D., associate member in the Infectious Diseases department at St.
Jude. "Eliminating these secondary infections could dramatically
reduce the sickness and death rates among susceptible populations such
as infants and the elderly." This new approach might also offer some
protection if the avian influenza virus, H5N1, sparks a pandemic among
humans, he added. McCullers is first author of the PLoS paper.

The investigators demonstrated in mice infected with S. pneumoniae
that lysin can eliminate these bacteria from the ear. The team
conducted their study in mice developed at St. Jude that represented
the first mouse model in which acute otitis media develops in a
similar way that it develops the disease in children. The mice were
treated by purified lysin that was prepared in the laboratory of
Vincent A. Fischetti, Ph.D., a professor and co-head of the Laboratory
of Bacterial Pathogenesis and Immunology at The Rockefeller
University. He was assisted by Jutta M. Loeffler, postdoctoral
associate. Fischetti is senior author of the PLoS paper.

The researchers developed a mouse model of acute otitis media by first
establishing colonization of S. pneumoniae in the noses of mice.
Scientists then infected some of the mice with influenza virus and
mock-infected others with a virus-free solution. Although all the mice
carried the bacteria in their noses, none of the mock-infected mice
developed acute otitis media, while 63 percent of mice receiving
influenza virus developed this middle ear infection.

In the second part of the study, the team treated bacteria-colonized
mice twice, four hours apart, with either lysin or a mock treatment of
fluid. The lysin treatment was 100 percent effective in preventing
acute otitis media in the 10 treated mice while 80 percent of mice
receiving the fake treatment developed the ear infection.

"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, Fischetti said. "This might truly be a
case in which an ounce of prevention would be worth a pound of cure."

Other authors of this paper include Åsa Karlström and Amy R. Iverson
(St. Jude).

This work was supported in part by the United States Public Health
Service and ALSAC.

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized
for its pioneering work in finding cures and saving children with
cancer and other catastrophic diseases. Founded by late entertainer
Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its
discoveries with scientific and medical communities around the world.
No family ever pays for treatments not covered by insurance, and
families without insurance are never asked to pay. St. Jude is
financially supported by ALSAC, its fundraising organization.