Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stopping MRSA Before It Becomes Dangerous Is Possible

07.12.2009
Most scientists believe that staph infections are caused by many bacterial cells that signal each other to emit toxins. The signaling process is called quorum sensing because many bacteria must be present to start the process.

But the Jeff Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein.

The Brinker group’s nonantibiotic approach may make it easier to treat staphylococci strains that have become drug resistant like the methicillin-resistant Staphylococcus aureus MRSA. The control of such strains is a formidable problem in hospitals.

“The good news is that by inhibiting the single cell’s signaling molecules with a small protein, we were able to suppress any genetic reprogramming into the bacterium’s more virulent form,” said Brinker. “Our work clearly showed the strategy worked.”

Brinker, with appointments at Sandia National Laboratories and the University of New Mexico, wrote about his group’s findings in the Nov. 22 issue of Nature Chemical Biology.

In the course of its experiments, the Brinker team achieved three firsts:

They isolated Staphylococcus aureus bacteria in individual, self-assembled nanoscale compartments. Isolation of an individual bacterium previously had been achieved only computationally, leaving open questions of how a physically and chemically isolated bacterium would actually behave.

They demonstrated that it was the release of signaling peptides from a single cell — not a quorum — that acted as a trigger to reprogram that same cell so that it released toxins.

By introducing an inexpensive, very low-density lipoprotein (VLDL) to bind to the messenger peptide, they stopped the single cell from reprogramming itself.

The term “quorum sensing” itself may prove a misnomer, the result of observations made in cell cultures rather than in the body, said Brinker. Because signaling molecules tend to diffuse away, a liquid culture of cells would naturally require many bacteria to produce enough signaling bacteria to begin reprogramming. The situation is otherwise in nature, where even a single cell may be sufficiently isolated that its own manufactured peptides would remain in its vicinity.

“Also, it’s hard to believe that one cell’s evolution could be based on what a whole bunch of cells do,” said Brinker. “When we instead consider that an individual cell will do what’s best for it, we can more clearly understand the benefits of that cell’s behavior.”

A bacterium may live longer by reprogramming itself to produce toxins or enzymes that allow it to access external nutrients, the Brinker group showed.

One aspect of experimental rigor was the team’s ability to organize living cells into a nanostructured matrix. “We’ve already done this with yeast,” said Brinker. “We just extended the process to bacteria.”

A key question was whether a cell could distinguish between peptides emitted by itself from those sent by other cells. If signaling peptides were chemically the same, what would it matter which bacterium emitted it?

As it turned out, said Brinker, “Peptides could bond to surface receptors on their own [generating] cell. So a single cell’s peptide molecules could activate its own genes to express proteins that make staph virulent.”

Indicating that the experiment had isolated the actual cause of the transformation, when the number of peptides produced by a cell ultimately came to exceed the number of lippoprotein molecules in solution, a stalled “quorum-sensing” procedure started up again.

When still more signaling molecules were added to the mix, the cell’s transformation occurred more rapidly.

Researchers hope to find a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. The problem could be solved, suggested Brinker, by the insertion of VLDL-bearing nanospheres (another Brinker-group creation) into the bloodstream, linked to a ‘searcher’ molecule designed to find and link to suspect peptides or cells that produce them.

“Inhibiting this specific signaling molecule from turning on virulence wouldn’t inhibit other bacteria,” Brinker said.

Targeting is important because the human gastro-intestinal system contains many useful bacteria. These are often decimated by conventional antibiotics but would be spared by the Brinker group’s method.

Brinker, a Sandia Fellow and distinguished professor of chemical engineering and molecular genetics and microbiology at UNM, performed this work with Eric Carnes and DeAnna Lopez at the UNM Department of Chemical and Nuclear Engineering (Lopez is now a Sandia technologist), Graham Timmins at the UNM College of Pharmacy, Niles Donegan and Ambrose Cheung at Dartmouth Medical School, and Hattie Gresham at the New Mexico Veterans Administration Health Care System.

The Sandia work is supported by the Basic Energy Sciences / Division of Materials Science and Engineering and Sandia’s Laboratory Directed Research and Development (LDRD) program. Other project work is supported by the Air Force Office of Scientific Research, the National Science Foundation, the Defense Threat Reduction Agency and the National Institutes of Health.

Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, an autonomous Lockheed Martin company, for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies, and economic competitiveness.

Neal Singer | Newswise Science News
Further information:
http://www.sandia.gov

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>