He and his team
took a bacteriophage cloned out the phage enzyme, known as the streptococcal
bacteriophage C1, which is specific for groups A, C and E streptococci. First they added a tiny
portion -- ten nannograms -- of the enzyme to ten million organisms in
a test tube. "In five seconds the organisms were all killed. The enzyme
just knocks holes in the cell wall. The bacteria explode. I was flabbergasted,"
says Fischetti.
The researchers
next conducted a basic animal study. They introduced a dose of the phage
enzyme into the oral cavity of mice, followed by a dose of live group A
streptococci. The enzyme protected against colonization -- only. 28.5 percent
of the mice given the enzyme became infected versus 70 percent of the untreated
animals. The study suggested the potential for eliminating the bacteria
from the upper respiratory mucosal tract, reducing the incidence or transmission
of related diseases. Because no safety problems surfaced
in the animal studies, Fischetti and his colleagues are looking forward
to Phase One trials in humans.
"Of course no
one has a crystal ball, and we will have to wait and see what happens when
you try this approach in humans, but it is very exciting work," says Dr.
Joseph Ferretti, a research professor
of microbiology and immunology at the University of Oklahoma Health Sciences
Center in Oklahoma City and a specialist in the study of streptococci. Ferretti points
out that the strategy may prove effective against streptococcal pneumonia,
which has a high incidence of antibiotic resistance.
Phage enzymes
developed for other strains of streptococci may one day be equally important.
Group B streptococcal infection affects as many as 40 percent of pregnant
women. The infection, if transmitted to the baby during birth, can cause
septicemia or neonatal meningitis, which can be fatal.
"Right now many
women must be given antibiotics in the third trimester, whereas eventually
we might simply be able to use a spray or a tampon soaked with the phage
enzyme and prevent transmission," says Fischetti.
He also envisions
the possible use -- in daycare centers or nursing homes -- of aerosol sprays,
perhaps twice a week, to prevent transmission of strep throat or pneumonia.
If the treatment
strategy is successful in humans, it will certainly be attempted with bacteria
other than streptococci. Right now the research suggests that the phage
enzyme can wipe out certain streptococci on contact on mucosal surfaces.
Fischetti is beginning studies to see if the enzyme can survive in blood.
He doubts that the enzyme can attack bacteria that survive intracellularly,
but no one knows.
"The approach
has restricted use and delivering the enzyme to the proper surfaces may
be difficult," says Dr. William Jacobs, professor of microbiology and immunology at Albert Einstein College
of Medicine. "For instance, with tuberculosis, getting it to all the tissue
in the lungs might be difficult. For now, the approach seems to work great
on strep, and that is wonderful."
Fischetti says
that while the enzyme might not cure TB, it might help prevent the transmission
of any bacteria, including tuberculosis, that can be transmitted by saliva.
Whether the
use of enzymes might trigger an antibody response in humans, or whether
there may be some element in serum that degrades the enzyme remains to
be seen.
"If it works,
it works," says Dr. John Robbins, Chief of the Laboratory for Developmental
and Molecular Immunity at the National Institutes of Health. "Everything
they are saying, I am for. but we will just have to see. Antibodies to
enzymes generally form very quickly. Still, this is an approach that is
different and there is no reason not to give it a fair trial."
Fischetti's
group has recently received a grant from the Defense Department,
partly because of the military's concern over controlling strep infection
among recruits.
Recruits currently receive
penicillin prophylactically, but antibiotic resistance has prompted a search
for alternative approaches.
However, preventing
strep throat, Fischetti believes, is not the only reason for the military's
interest. "They see the possibility that phage enzymes could be used as
a way of countering organisms used in biowarfare, like anthrax or plague,"
he said.
So, too, have
Russian investigators, with whom Fischetti's team is beginning to cooperate.
Russians have studied bacteriophages for years, although -- as Fischetti
hastens to point out -- they never thought of using the phage enzymes to
wipe out bacteria. "We are now able to help each other," he says. "They
have many bacteriophages, and we are able to identify the gene for the
specific enzyme."
--
Copyright
2001 by United Press International.
All
rights reserved.
--
