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Princeton team learns why some drugs pack such a punch
Date:8/20/2009

constructed proteins stuck to the ribosome, jamming the translocator in the bacteria.

"This is very similar to plugging the translocator with a folded protein and, sure enough, this also causes translocator destruction," Silhavy said. "It's like putting an anchor on the spaghetti instead of a knot. They are stuck and dead forever."

Researchers had been confused as to why these antibiotics seemed to be so adept at killing some kinds of bacteria more quickly than others. These experiments provide an explanation. Translocators are essential for life and, if some bacteria have fewer translocators from the start, then they are more vulnerable to such an attack.

"While it has been known for many years that these antibiotics work by inhibiting bacterial protein synthesis, it was not clear why some bacteria in a population appeared more susceptible than others," van Stelten said. "Our work has identified a new reason why these antibiotics are lethal to bacteria that may help explain these earlier findings."

The researchers made their discovery not because of a new piece of equipment or a new technique. "Like the vast majority of advancements in science and medicine, we happened upon this remarkable answer through basic research," van Stelten said.

The finding could have important implications for medicine.

"If we are to have any hope of outpacing the antibiotic resistance obtained by bacteria, it is paramount that we fully understand the mechanism of action of the antibiotics we currently use," van Stelten said. "Unfortunately, this is often very difficult as evidenced by the fact that, 50 years on, we are still learning new things about them."

Their work also produced another important result. When the translocators in bacteria became jammed by errant proteins, the researchers observed that the translocators emitted a molecular signal -- a stress response -- that called in a destructive enzyme known as the F
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Contact: Kitta MacPherson
kittamac@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

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