Mar 29, 2007    #038
Contact: Noemi Rojas

Research could result in new treatments for autoimmune disorders and common infectionsStudy published in Nature Immunology

University of Missouri-Kansas City researcher Brian Geisbrecht, Ph.D., has discovered how the pathogen Staphylococcus aureus (S. aureus) disables an essential component of the human immune system. S. aureus is a leading cause of community acquired and hospital-related infections. These so-called "Staph infections" are widely regarded as a growing threat to public health as the incidence of antibiotic-resistant strains continues to climb.

To overcome S. aureus infection, the body requires immune molecules called complement proteins. These proteins circulate in the bloodstream as inactive precursors and represent the first line of defense against invading microbes. Upon encountering invading microbes such as Staphylococcus, complement proteins are processed into smaller subunits that summon more immune cells and trigger other downstream defense mechanisms.

S. aureus produces a protein, called Efb, which suppresses activation of the complement response, and Geisbrecht and fellow researcher John D. Lambris, Ph.D., from the University of Pennsylvania School of Medicine have discovered how this happens.

In a study published in this month's issue of Nature Immunology, Geisbrecht’s and Lambris’ research has shown that Efb changes the shape of complement proteins. This change prevents the proteins from being cleaved into the smaller subunits, and renders the complement response ineffective. In turn, this prevents both the destruction of microbe and recruitment of more immune cells to the site of infection.

Geisbrecht and Lambris hope their research can be used to keep Efb from altering and preventing the complement protein activation process. Even though this may result in an important new class of antibiotics, the scientists believe that there may be more to the story.

"While complement is an important component of healthy immune systems, other studies have shown that over-activation of complement proteins can contribute to autoimmune diseases, such as lupus, and to the damage of healthy tissue following either transplantation or loss of circulation, as is seen in heart attacks,” Geisbrecht said. “By studying the properties of bacterial anti-inflammatory proteins, such as Efb, we may eventually identify new approaches to treating these diseases through clinical inhibition of the complement response.”

“Brian is one of our truly talented young scientists at the School of Biological Sciences,” Lawrence Dreyfus, Ph.D., dean of the SBS, said. “His most recent discovery detailing the structure of the Efb-complement C3 complex is a milestone in our understanding of how Staphyloccus aureus, a significant cause of human disease and death, is able to circumvent our innate immunity and establish an infection. Brian is one growing cadre of structural biology researchers at the School who are presently researching some of the most fundamental problems in molecular biology. We are very fortunate to have Brian as one of our own and look forward to his continued success.”

“These findings are a major step forward in life sciences research,” John Baumann, Ph.D., vice provost for research at UMKC, said. “Dr. Geisbrecht is one of UMKC’s many bright, young researchers and we’re fortunate to have his skills and expertise on our team.”

Geisbrecht is an assistant professor. He joined the faculty of the School of Biological Sciences in 2004 after completing post-doctoral studies in structural biology the Department of Biophysics and Biophysical Chemistry at the Johns Hopkins University School of Medicine in Baltimore, MD. Geisbrecht was awarded a biological chemistry from the same institution in 2000, and graduated with a B.S. in chemistry/biochemistry from Saint Vincent College in Latrobe, PA in 1996.

The University of Missouri-Kansas City (UMKC), one of four University of Missouri campuses, is a public university serving more than 14,000 undergraduate, graduate and professional students. UMKC engages with the community and economy based on a three-part mission: visual and performing arts, health and life sciences, and urban affairs.


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