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Newly designed molecule blocks chlamydia bacteria
Date:7/20/2011

er the whole cell and prevents it from mounting an effective, pathogen-killing immune response," Valdivia said. "Chlamydia is unique among pathogens, in that it can co-exist within humans without causing symptoms for a long time. This reflects a careful balance between the host and the pathogen. We think CPAF is central to this balance. Therefore, if we disarm it, we can tilt the equation toward the human host and mount an effective immune response that will not only clear the infection but prevent it from re-emerging."

The Duke chemists, led by Dewey McCafferty, Ph.D., a professor in the Duke Departments of Chemistry and Biochemistry, designed a molecule that could block the CPAF activity inside of human cells.

"Typically, to design a potent, specific, and cell-permeable inhibitor is a complicated undertaking and inhibitor designs don't work right away," McCafferty said. "But in this case, it worked on the first try. Professor Valdivia's group of microbiologists and my group of chemical biologists worked to establish which qualities we needed to incorporate into a CPAF inhibitor. The results are very exciting, because we have an inhibitor lead molecule that may form the basis for a new class of anti-Chlamydial drugs."

They found that when CPAF was blocked over time by their designed molecule, the protective home that the bacteria make for themselves within the infected cells degraded, and CPAF no longer could degrade the proteins in the cell that would normally mount an immune response to the infection.

When CPAF is inhibited, the infected human cells effectively "commit suicide," Valdivia said. "When the infected human cell dies, so does Chlamydia, and this ends the infection."

Valdivia said that the findings could yield new therapeutic approaches that might turn a natural infection into a vaccination.

"By stopping the cloaking response of the bacteria, we are essentially revealing where they ar
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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