J. Wang et al., "Platensimycin is a selective FabF inhibitor with potent antibiotic properties," Nature, 441:358-61, 2006. (Cited in 91 papers)
Sifting through South African soil samples, scientists at Merck Research Laboratories found a new compound called platensimycin. It is effective against methicillin-resistant Staphylococcus aureus and other multiple-drug-resistant bacteria, thus representing an entirely new class of antibiotic. The researchers used X-ray crystallography and direct-binding assays to show that platensimycin kills bacteria by binding to a key intermediate, called FabF, in enzyme-mediated lipid construction, thus short-circuiting bacterial fatty acid synthesis.
The method of action:
Eric Brown, a biochemist at McMaster University in Canada, hails the Merck team's multidisciplinary approach to revealing platensimycin's mode of action. "It's very difficult, for example, to show that a small molecule would have an affinity for an intermediate in an enzyme-driven reaction," he says.
Last year, Nicolaou and colleagues synthesized carbaplatensimycin, a platensimycin analog that shows similar antibiotic potency. Though platensimycin may be the latest weapon against drug-resistant bacteria, Nicolaou warns: "I doubt that this will be the end of the war against bacteria."
|Platensimycin vs. Linezolid (minimum inhibitory concentration)|
|S. aureus (MSSA)||0.5 μg/ml||4 μg/ml|
|S. aureus (MRSA)||0.5 μg/ml||2 μg/ml|
|Enterococcus faecium (vancomycin-resistant)||0.1 μg/ml||2 μg/ml|
Correction (posted May 23): When originally posted, the story referenced μg/ml incorrectly as mg/ml. That correct reference is μg/ml. The references have been corrected, and The Scientist regrets the errors.