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Scientists investigate alternative to antibiotic treatment

Dr. Frank DeLeo, chief of NIAID’s Laboratory of Bacteriology and an expert in neutrophil biology and bacterial pathogenesis. A graduate of Seeley Swan High School and Montana State University, DeLeo has worked at Rocky Mountain Laboratory since 2000.

By Michael Howell

Scientists at Rocky Mountain Laboratory (RML) in Hamilton, a division of the National Institute of Allergy and Infectious Diseases (NIAID), working with colleagues from New Jersey Medical School-Rutgers University, are making headway in their investigation of an anti-body based treatment for at least one kind of bacterial infection that has developed a resistance to antibiotics. The bacteria, called Klebsiella, causes about 10 percent of all hospital-acquired infections in the United States. This strain of bacteria is particularly concerning because it is resistant to most antibiotics.
The bacteria is in the ecoli family and commonly found in the guts of healthy humans. However, in people with compromised immune systems, undergoing organ transplant, or taking chemotherapy, the bacteria can enter the bloodstream, resulting in serious infection. Once the bacteria enters the bloodstream there is only a 50/50 chance of survival. Antibiotic treatment is the most common form of treatment for bacterial infections of this sort.
According to RML’s Dr. Frank DeLeo, chief of NIAID’s Laboratory of Bacteriology and an expert in neutrophil biology and bacterial pathogenesis who is leading the study, antibiotics directly attack the bacteria, either killing it or at least inhibiting its growth by blocking protein synthesis or by blocking the bacteria’s ability to make a new cell wall, in which case it ruptures and dies. In most cases of ecoli infection this treatment is used successfully.
But when a bacteria, like Klebsiella, becomes antibiotic resistant, an alternative treatment is required and that’s where the latest research into the body’s natural immune system response comes into play.
“What we’ve been doing for a couple of years now is trying to understand how a healthy person defends against this specific bug,” said Dr. DeLeo.
According to DeLeo the release of antibodies is part of the body’s natural defense system. An antibody is a protein found in the blood in low levels. But when it finds something it recognizes as a threat, it not only tries to defend against it, it calls in reinforcements, and the number of antibodies multiplies.
Studies of modified human blood samples showed that a component of the innate immune system called the complement system is pivotal to killing this particular bacteria. The complement system includes nine proteins (C1-9) that help protect against bacterial infections, a process aided by antibodies.
Their recent study determined that killing of this bacteria corresponds with a portion of the complement system known as the membrane attack complex, which contacts bacterial surfaces. Blood depleted of antibodies and/or the complement system had a significantly reduced ability to kill the antibiotic-resistant bacteria.
What keeps the bacteria from being affected by white blood cells, which normally attack and kill such bacteria, is a sugar coating that provides a protective shell. It is the natural antibodies in the system that provide the key to dissolving that protective covering and allowing the white blood cells to do their job.
The next step in the process is to identify a specific antibody that works in this case and develop a vaccine.
“In essence, it is a way to boost the body’s innate immune defense system,” said DeLeo. The next step involves production of some purified quantities of the sugar coating that can be used in rabbits to elicit an antibody response. This could then potentially be used to manufacture a vaccine for humans.

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