|A Deadly Foe
Friend or foe?
What makes airborne tularemia so fascinating to researchers
is its deceptiveness. “When Francisella bacteria first enter
the body, they are not eliminated by the body’s natural
defense system,” Klose says. Like an enemy hiding in a
Trojan horse, they turn deadly once accepted into the fold.
Normally, when bacteria enter the body, macrophages, a type of white blood cell, are the first line of defense. “The macrophages engulf the invaders and destroy them, then scour the body looking for more,” he says. “Then, they teach the body that the invaders are bad and help the body develop immunity.”
But that doesn’t happen with tularemia. Instead, the macrophages engulf the bacteria, but don’t kill them. As the macrophages patrol throughout the body, the tularemia breeds inside of them. Then the macrophages burst, spreading the tularemia to distant areas, where they cause widespread infection.
“What we want to find out is how does tularemia prevent itself from being killed by macrophages when it enters the body,” Klose says. “We’ve identified certain genes that play a part in the process, but we don’t yet know what these genes do. Once we figure it out, we want to develop potential
Because of the work’s deadly implications, access to organisms for
research is under tight control, he adds.
The two NIAID awards given for UTSA’s tularemia research
have one goal: to identify potential vaccine candidates to
work against the disease. One is a program project grant
to conduct basic research on the organism, while the other is part of a large government contract involving three
universities and two companies.
The first grant was awarded in July 2005. The $6.4
million, five-year project is made up of four interdependent projects conducted by Klose, Arulanandam and Teale, as well as Michael Berton, a microbiologist from the University of Texas Health Science Center at San Antonio (UTHSCSA).
Klose studies the organism to identify the genes responsible for its ability to cause the disease. Inactivating these genes in tularemia converts them from dangerous to benign
organisms, which then become potential vaccine candidates. Klose then passes them along to Arulanandam. “I am studying
which of the vaccine candidates gives us the best immune response and protection,” Arulanandam says. “We have already tested some of them, and some look very promising.”
Meanwhile, Teale’s research focuses on the mechanisms that the bacteria use to avoid being killed by the body’s
natural defenses, while Berton focuses on the body’s natural defense system to find out why the body does not recognize tularemia as a dangerous invader.
The second grant, awarded in August 2005, is part of
a large, five-year government contract to produce tularemia
vaccine candidates. “This is a more focused approach
involving a national consortium of scientists with the
goal of producing a tularemia vaccine within five years,” Klose says.
He and Arulanandam are working on the $1.9 million project. “We have a list of targeted antigens that Dr. Klose will mutate, then I will take those and test them in the lab,” Arulanandam says.
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