Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Unveil Molecular Details of How Bacteria Propagate Antibiotic Resistance

30.07.2012
Fighting “superbugs” – strains of pathogenic bacteria that are impervious to the antibiotics that subdued their predecessor generations – has required physicians to seek new and more powerful drugs for their arsenals.

Unfortunately, in time, these treatments also can fall prey to the same microbial ability to become drug resistant. Now, a research team at the University of North Carolina at Chapel Hill (UNC) may have found a way to break the cycle that doesn’t demand the deployment of a next-generation medical therapy: preventing “superbugs” from genetically propagating drug resistance.

The team will present their findings at the annual meeting of the American Crystallographic Association (ACA), held July 28 – Aug. 1 in Boston, Mass.

For years, the drug vancomycin has been the last-stand treatment for life-threatening cases of methicilin-resistant Staphylococcus aureus, or MRSA. A powerful antibiotic first isolated in 1953 from soil collected in the jungles of Borneo, vancomycin works by inhibiting formation of the S. aureus cell wall so that it cannot provide structural support and protection. In 2002, however, a strain of S. aureus was isolated from a diabetic kidney dialysis patient. This particular strain would not succumb to vancomycin. This was the first recorded instance in the United States of vancomycin-resistant Staphylococcus aureus, or VRSA, a deadly variant that many now consider one of the most dangerous bacteria in the world.

Former UNC graduate student Jonathan Edwards (now at the Massachusetts Institute of Technology), under the guidance of chemistry professor Matthew Redinbo, led the research team that sought a detailed biochemical understanding of the VRSA threat. They focused on a S. aureus plasmid – a circular loop of double-stranded DNA within the Staph cell separate from the genome – called plW1043 that codes for drug resistance and can be transferred via conjugation (“mating” that involves genetic material passing through a tube from a donor bacterium to a recipient).

Before the plasmid gene for drug resistance can be passed, it must be processed for the transfer. This occurs when a protein called the Nicking Enzyme of Staphylococci, or NES, binds with its active area, known as the relaxase region, to the donor cell plasmid. NES then cuts, or “nicks,” one strand of the double helix so that it separates into two single strands of DNA. One moves into the recipient cell while the other remains with the donor. After the two strands are replicated, NES reforms the plasmid in both cells, creating two drug-resistant Staph cells that are ready to spread their misery further.

Using X-ray crystallography, Edwards, Redinbo, and their colleagues defined the structure of both ends of the VRSA NES protein, the N-terminus where the relaxase region resides and the molecule’s opposite end known as the C-terminus. They noticed that the N-terminus structure included a region with two distinct protein loops. Suspecting that this area might play a critical role in the VRSA plasmid transfer process, the researchers cut out the loops. This kept the NES relaxase region from clamping onto or staying bound to the plasmid DNA.

Biochemical assays showed that the function of the loops was indeed to keep the relaxase region attached to the plasmid until nicking occurred. This took place, the researchers learned, in the minor groove of a specific DNA sequence on the plasmid.

“We realized that a compound that could block this groove, prevent the NES loops from attaching and inhibit the cleaving of the plasmid DNA into single strands could potentially stop conjugal transfer of drug resistance altogether,” Edwards says.

To test their theory in the laboratory, the researchers used a Hoechst compound – a blue fluorescent dye used to stain DNA – that could bind to the minor groove. As predicted, blocking the grove prevented nicking of the plasmid DNA sequence.

Redinbo says that this “proof of concept” experiment suggests that the same inhibition might be possible in vivo. “Perhaps by targeting the DNA minor groove, we might make antibiotics more effective against VRSA and other drug-resistant bacteria,” he says.

This news release was prepared for the American Crystallographic Association (ACA) by the American Institute of Physics (AIP).

MORE INFORMATION ABOUT THE 2012 ACA MEETINGThe ACA is the largest professional society for crystallography in the United States, and this is its main meeting. All scientific sessions, workshops, poster sessions, and events will be held at the Westin Waterfront Hotel in Boston, Mass.

USEFUL LINKS:
Main meeting website: http://www.amercrystalassn.org/2012-meeting-homepage
Meeting program: http://www.amercrystalassn.org/2012-tentative-program
Meeting abstracts: http://www.amercrystalassn.org/app/sessions
Exhibits: http://www.amercrystalassn.org/2012-exhibits
ABOUT ACA
The American Crystallographic Association (ACA) was founded in 1949 through a merger of the American Society for X-Ray and Electron Diffraction (ASXRED) and the Crystallographic Society of America (CSA). The objective of the ACA is to promote interactions among scientists who study the structure of matter at atomic (or near atomic) resolution. These interactions will advance experimental and computational aspects of crystallography and diffraction. They will also promote the study of the arrangements of atoms and molecules in matter and the nature of the forces that both control and result from them.

Catherine Meyers | Newswise Science News
Further information:
http://www.aip.org
http://www.buffalo.edu

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>