Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers unzip MRSA and discover route for vaccine

18.01.2011
URMC team presents latest data at National Orthopaedics Meeting

University of Rochester Medical Center orthopaedic scientists are a step closer to developing a vaccine to prevent life-threatening methicillin-resistant staphylococcus aureus (MRSA) infections following bone and joint surgery.

Other MRSA vaccine research has failed to produce a viable option for patients because of the inability to identify an agent that can break through the deadly bacteria's unique armor. Most other research has targeted the surface of the bacteria, but the URMC team discovered an antibody that reaches beyond the microbe's surface and can stop the MRSA bacteria from growing, at least in mice and in cell cultures.

The Orthopaedic Research Society invited URMC researchers to present their findings on Jan. 16, 2011, at the ORS annual meeting in Long Beach, Calif. The team is led by Edward M. Schwarz, Ph.D., professor of Orthopaedics and associate director of the URMC Center for Musculoskeletal Research. John Varrone, a second-year graduate student in Schwarz's lab, will discuss the data at ORS and the ongoing search for attractive molecular candidates for use in a vaccine.

Staph infection is the leading cause of osteomyelitis, a serious bacterial infection of the bone. Up to half of these infections are due to MRSA, a particular strain of staph known as a "superbug" because of its antibiotic resistance. MRSA causes nearly 500,000 hospitalizations and 19,000 deaths a year in the United States. Although improvements in surgical techniques and use of prophylactic antibiotics prevents some MRSA infections, osteomyelitis is expected to remain a serious problem in the future as people live longer and request more joint replacements and reconstructive surgery.

Management of MRSA infections due to bone and joint surgery is very challenging, Schwarz said, and therefore a vaccine to prevent the infection is badly needed.

It is difficult to pin down the source of most post-surgical MRSA infections, but the health and financial consequences are severe. Hospital stays can last up to six months. Standard treatment includes removing the MRSA-colonized prosthetic joint replacement, then an extensive washing and draining of the infected area in an attempt to clear out all bacteria before it seeds in nearby tissue and bone. Antibiotic spacers are usually placed near the joint for six to eight weeks.

A second joint replacement is an option only if the antibiotic-spacer treatment is successful and the health of the patient remains stable. However, the re-infection rate is very high (40 to 50 percent) and remains a risk for months or even years after the initial assault. In some cases the patient never fully regains the use of the infected joint, said Regis O'Keefe, chief of Orthopaedics at URMC and an expert in the treatment of MRSA.

"It's essential that we have mechanisms in place to prevent this awful infection," O'Keefe said. "We are very excited about our vaccine research. It'll have a phenomenal impact on individuals locally and across the country if we are successful."

Breaking the Zipper

Schwarz, Varrone, and colleagues hypothesized that the best way to attack staph aureus was to target the glucosaminidase (Gmd) protein contained in the deadly bug. Gmd is known to act as a zipper on the bacteria, opening the impenetrable armor (cell wall) during cell division. In the absence of Gmd, staph aureus cannot replicate efficiently, dramatically reducing its ability to cause infections. Thus, if they could find an agent that inhibits bacterial growth and prevents the cell wall from closing during binary fission, Schwarz reasoned, perhaps the bacteria itself could be destroyed.

The abstract presented at ORS describes two key findings. First, the Schwarz lab discovered four anti-Gmd monoclonal antibodies that disrupt the growth of MRSA bacteria in cell cultures, by breaking the zipper and preventing cell division. The team also demonstrated exactly how the antibody works. Since MRSA is inclined to grow rapidly, as single cells, they sought an antigen that forced the bacteria cells to clump. Electron microscopy images of the bacteria exposed to the anti-Gmd antibodies show evidence of exploding staph; however, additional research is being done to confirm this mechanism of action.

Second, researchers demonstrated that when mice were infused with the anti-Gmd antibody, and then exposed to MRSA, only about half of the mice developed the infection. As expected, Schwarz said, protection was dependent upon vaccine dose, with the lowest dose offering the least amount of protection.

"A vaccine in humans would probably not be a foolproof approach to preventing infection 100 percent of the time," Schwarz said. "However, even if we could reduce the risk of MRSA by 35 percent, that would be an enormous improvement in the field."

Researchers are seeking anti-Gmd agents with the best properties for binding to Gmd and making the bacteria less viable. This work is being led by scientists at Codevax LLC, a company started by the University of Rochester and private venture capitalists to co-develop and promote unlicensed vaccine technologies for infectious diseases. John Daiss, a scientist at Codevax, is leading the effort to find existing monoclonal antibodies with strong safety profiles – such as those used to develop the cancer drugs Herceptin and Rituxan – so that researcher can move quickly from the bench to initial clinical trials, Schwarz said.

Stephen Dewhurst, Ph.D., chair and dean's professor of Microbiology and Immunology at URMC is president of Codevax. John Daiss is employed by Codevax. Edward Schwarz, John Varrone and Regis O'Keefe do not have a financial interest in the company, however, the University of Rochester holds an equity interest in Codevax.

The MRSA vaccine project is funded, in part, by Codevax. Additional funding was provided by URMC Musculoskeletal Research, URMC Technology Development Grant, and the U.S. Department of Health and Human Services.

Leslie Orr | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown 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: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>