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Bacterial walls come tumbling down

The first detailed images of an elusive drug target on the outer wall of bacteria may provide scientists with enough new information to aid design of novel antibiotics. The drugs are much needed to treat deadly infections initiated by Staphylococcus aureus and other bacterial pathogens.

The research team, led by Natalie Strynadka, a Howard Hughes Medical Institute (HHMI) international research scholar at the University of British Columbia in Vancouver, Canada, published its findings in the March 9, 2007, issue of the journal Science.

Penicillin and many newer antibiotics work by blocking a piece of the machinery bacteria use to construct their durable outer walls. Without these tough, protective coatings, bacteria die. The enzymatic machinery (known as PBP2) studied by Strynadka's group has two main parts: One end assembles long sugar fibers; the other end stitches them together with bits of protein to form a sturdy interlocking mesh shell.

Strynadka's team has provided a long-awaited look at the portion of the enzyme used in the first step of the biochemical pathway that initiates assembly of the sugar coating. The second step is targeted by penicillin and has been well studied.

Although scientists have spent many years identifying bacterial components whose structural features might have weaknesses that can be exploited by antibiotics, progress in turning up bona fide drug targets has been slow. The cell wall enzymes in particular have tantalized scientists, Strynadka said. "The cell wall has all the hallmarks of a great drug target," she explained. "It is essential to the survival of all bacteria. The enzymes that create the cell wall are unique to bacteria. And it is accessible; you don't have to get the antibiotics into the cell."

In their structural studies, the researchers focused on Staphylococcus aureus, a notorious human pathogen. An epidemic strain of the bacteria known as methicillin-resistant Staphy
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
9-Mar-2007


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