Researchers identify mechanism by which vancomycin resistance spreads between bacteria

Published on January 31, 2013 at 2:59 AM · No Comments

Worldwide, many strains of the bacterium Staphyloccocus aureus, commonly known as staph infections, are already resistant to all antibiotics except vancomycin. But as bacteria are becoming resistant to this once powerful antidote, S. aureus has moved one step closer to becoming an unstoppable killer. Now, researchers at the University of North Carolina at Chapel Hill have not only identified the mechanism by which vancomycin resistance spreads from one bacterium to the next, but also have suggested ways to potentially stop the transfer.

The work, led by Matthew Redinbo, professor of chemistry at UNC's College of Arts and Sciences, addresses the looming threat of incurable staph infections - a global public health problem that has mobilized scientists across disciplines to work together to identify the Achilles heel of these antibiotic-resistant bacteria.

"We used to live in a world where antibiotics could readily cure bacterial disease," said Redinbo. "But this is clearly no longer the case. We need to understand how bacteria obtain resistance to drugs like vancomycin, which served for decades as the 'antibiotic of last resort.'"

In his work, Redinbo and his team targeted a bacterial enzyme known as Nicking Enzyme in Staphyloccoccus, or NES. The enzyme has long been known to interact with plasmids, circular pieces of double-stranded DNA within bacteria that are physically separate from the bacterial chromosome. Plasmids commonly contain antibiotic-resistance genes, and can make the machinery necessary to transfer these genes from an infected bacterium to an uninfected one.

By revealing the crystal structure of NES, the researchers found that this enzyme nicks one strand of the plasmid at a very specific site-and in a very specific way. It turns out that NES forms two loops that work together to pinch one strand of the plasmid at a particular groove in the DNA to cut it. This strand is now free to leave its host and transfer to a nearby bacterium, making them resistant to vancomycin.

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