Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new model -- and possible treatment -- for staph bone infections

20.06.2013
Osteomyelitis – a debilitating bone infection most frequently caused by Staphylococcus aureus ("staph") bacteria – is particularly challenging to treat.
Now, Vanderbilt microbiologist Eric Skaar, Ph.D., MPH, and colleagues have identified a staph-killing compound that may be an effective treatment for osteomyelitis, and they have developed a new mouse model that will be useful for testing this compound and for generating additional therapeutic strategies.

James Cassat, M.D., Ph.D., a fellow in Pediatric Infectious Diseases who is interested in improving treatments for children with bone infections, led the mouse model studies. Working with colleagues in the Vanderbilt Center for Bone Biology and the Vanderbilt University Institute of Imaging Science, Cassat developed micro-computed tomography (micro-CT) imaging technologies to visualize a surgically introduced bone infection in progress.

"The micro-CT gives excellent resolution images of the damage that's being done to the bone," said Skaar, the Ernest W. Goodpasture Professor of Pathology. "We found that staph is not only destroying bone, but it's also promoting new bone growth. Staph is causing profound changes in bone remodeling."

Cassat also established methods for recovering – and counting – bacteria from the infected bone.

"We're not aware of any other bone infection models where you can pull the bacteria out of a bone and count them in a highly reproducible manner," Skaar said. "From a therapeutic development standpoint, we think this model is going to allow investigators to test new compounds for efficacy against bone infections caused by staph or any other bacteria that cause osteomyelitis."

Several pharmaceutical companies have already approached Skaar and his team about testing compounds in the new bone infection model, which the investigators describe in the June 12 issue of Cell Host & Microbe.

Using the model, the team demonstrated that a certain protein secreted by staph plays a critical role in the pathogenesis of osteomyelitis. Understanding the specific bacterial factors – and the bone cell signals – that promote bone destruction and formation during infection could lead to new strategies for restoring bone balance, Skaar said.

"Even if it's not possible to kill the bacteria, compounds that manipulate bone growth or destruction might have some therapeutic benefit."

Still, Skaar is interested in treatments that will eliminate the infection.

The staph bacteria involved in osteomyelitis and in other persistent infections (such as lung infections in cystic fibrosis) are often a sub-class of staph known as "small colony variants." These staph variants grow slowly and are resistant to entire classes of antibiotics commonly used to treat bone and lung infections, Skaar said.

One way that staph bacteria become antibiotic-resistant small colony variants is by changing the way they generate energy. Instead of using respiration, they switch to fermentation, which blocks antibiotic entry and slows bacterial growth.

In a high-throughput screen for compounds that activate a heme-sensing bacterial pathway, graduate student Laura Mike identified a compound that kills fermenting staph. The findings are reported in the May 14 issue of the Proceedings of the National Academy of Sciences.

"This is a completely new molecular activity," Skaar said. "We don't know of other molecules that are toxic against fermenting bacteria."

The compound – and derivatives synthesized by Gary Sulikowski, Ph.D., and his team – might be useful in treating staph small colony variants, or in preventing their emergence.

The investigators demonstrated in culture that treating staph with the antibiotic gentamicin forced it to become a small colony variant and ferment, and that co-treatment with the new compound prevented resistance and killed all of the bacteria.

"We think a really interesting therapeutic strategy for this compound is that it might augment the antimicrobial activity of existing classes of antibiotics by preventing resistance to them – it might extend the lifetime of these classes of antibiotics," Skaar said.

This would be similar to the drug Augmentin, which combines a traditional penicillin-type antibiotic and a compound that blocks bacterial resistance.

The investigators are excited to test the new compound in the mouse model of osteomyelitis. First, they will treat the mice with gentamicin and assess whether staph small colony variants form. If so, they will co-administer the new compound to test if it prevents resistance, and they will also assess it as a single treatment for the persistent infection.

Skaar stressed that Vanderbilt's collaborative environment made these studies possible. Daniel Perrien, Ph.D., and Florent Elefteriou, Ph.D., in the Vanderbilt Center for Bone Biology and colleagues in the Vanderbilt University Institute of Imaging Science were critical in facilitating development of the bone infection model. Sulikowski and other colleagues in the Vanderbilt Institute of Chemical Biology (VICB) enabled the compound development.

"This is exactly the kind of work the VICB is promoting – getting biologists like me together with chemists, to make new therapeutics," Skaar said.

The research was supported by the Searle Scholars Program and grants from the National Institutes of Health (AI069233, AI073843, RR027631, AI091856, HD060554), including the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense (AI057157).

Leigh MacMillan | EurekAlert!
Further information:
http://www.vanderbilt.edu

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

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

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>