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Insect antibiotics Resistance is futile!

(Philadelphia, PA) For antibiotics, the best way to beat bacterial defenses may be to avoid them altogether. Researchers at University of Pennsylvania School of Medicine have discovered that Cecropin A, a member of a family of antibiotic proteins produced by insects, may kill bacteria and avoid resistance by entering bacterial cells and taking control of their genetic machinery.

While most antibiotics kill bacteria by attacking critical enzyme systems, Cecropin A somehow slips inside the bacteria and turns specific genes on and off. The findings challenge conventional thinking on how these antibiotics function, and may aid in turning antimicrobial peptides like Cecropin A into therapeutic agents.

"For decades, researchers have studied Cecropin A and focused on its obvious effects against bacterial cell walls and membranes. These antibiotics certainly do disrupt outer structures of the bacterial cell, but there's much more to the story," said Paul H. Axelsen, M.D., an associate professor in the Department of Pharmacology and Division of Infectious Diseases at Penn. "Before the bacterial cell dies, Cecropin A enters the cell and alters the way its genes are regulated. It's like sneaking over the castle wall and opening the gates from the inside. We need to understand this mechanism of action because it may explain why bacteria are unable to develop resistance to this family of antibiotics."

Axelsen's findings were described in the January issue of the Antimicrobial Agents and Chemotherapy, a publication of the American Society for Microbiology. In their study, Axelsen and his colleagues treated E. coli with small doses of Cecropin A not enough to kill the bacteria, but enough to see what genes are affected when bacteria are exposed to the antibiotic. They found that transcript levels for 26 genes are affected, 11 of which code for proteins whose functions are unknown. Even more surprising for the researchers, the genes are not the same as the ones
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Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
6-Feb-2003


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