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.
Moreover, Redinbo was able to capture a snapshot of the enzyme bound to the plasmid. “As a structural biologist, it’s all about the pictures for me,” said Redinbo. “And it was this picture that confirmed the precise location on which NES works.”
With this information, Redinbo knew the groove on the DNA that the enzyme recognize and could design a small synthetic molecule that would sit on this groove and block NES. Teaming up with colleagues at the California Institute of Technology, Redinbo did just that. The molecule prevented NES from nicking the DNA, which could prevent the resistance genes from spreading.
According to Redinbo and colleagues, this small synthetic molecule could help guide future research aimed at developing effective therapies for strains of antibiotic-resistant S. aureus.
“This is really exciting for us,” said Redinbo, who is also a professor at UNC’s School of Medicine and a member of the Lineberger Comprehensive Cancer Center. “It opens the door for potentially stopping the spread of antibiotic resistance—and that’s exactly what we need in this post-antibiotic era.”
The work was published this week in the online early edition of the Proceedings of the National Academy of Sciences.
Media note: Matthew Redinbo can be contacted at (919) 962-4504, email@example.com
College of Arts and Sciences contact: Dee Reid, (919) 843-6339, firstname.lastname@example.org
News Services contact: Thania Benios, (919) 962-8596, email@example.com
Thania Benios | Source: EurekAlert!
Further information: www.unc.edu
More articles from Life Sciences:
New genetic research finds shark, human proteins stunningly similar
06.12.2013 | Cornell University
Prostate cancer biomarker may predict patient outcomes
06.12.2013 | Vanderbilt University Medical Center
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
A genetic defect protects mice from infection with influenza viruses
A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses.
The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and ...
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
06.12.2013 | Materials Sciences
06.12.2013 | Life Sciences
06.12.2013 | Life Sciences
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News