New class of anti-bacterial drugs against MRSA discovered

October 2, 2012

Researchers at The Ohio State University have discovered a new class of treatment against methicillin-resistant Staphylococcus aureus (MRSA) as well as evidence of a growing need to quickly genotype individual strains of the organism most commonly referred to as the "superbug."

The two separate studies were funded by the Ohio State Center for Clinical and Translational Science (CCTS) with a goal of increasing the MRSA knowledge-base from both a basic science "bench" perspective, as well as using real-time data from infected communities to determine how MRSA spreads.

"The public is most familiar with the dramatic progression of skin infections caused by MRSA, but MRSA is responsible for a range of difficult to treat illnesses," noted Dr. Kurt B. Stevenson, professor of Infectious Diseases at the Ohio State College of Medicine, and primary investigator of the CCTS-funded study following the transmission of MRSA infections in communities. "While we've seen a decrease in the number of MRSA cases, identifying new agents and tracking methods will be critical to stopping these infections before they can start."

Cancer treatment search leads to potential MRSA killer, immune booster

In 2002, Ching Shih Chen, professor of at Ohio State College of Pharmacy, and a team of researchers were creating a library of anti- built around the scaffold of the molecules of celecoxib, a popular arthritis treatment in a family of drugs known as cyclooxygenase-2 (COX-2) inhibitors. This effort yielded OSU-03012 (AR12), a compound that is currently in a Phase I clinical trial as anticancer agent at the OSU Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

After observing how the substance acted within , Hao-Chieh Chiu, a then postdoctoral researcher in Chen's lab, realized that the derivatives were suppressing a mechanism that bacteria also use to take over their host cells. Chiu decided, with the support of Dr. Chen, to focus his research on testing the COX-2 compound library against a variety of bacteria.

"When the compounds showed anti-bacterial activity against Salmonella and Francisella, we began testing efficacy against a variety of pathogenic bacteria, including Staphylococcus aureus, Enterococcus, and Streptococcus," said Chiu, who is an assistant professor at the Department of Clinical Laboratory Sciences and Medical Biotechnology at National Taiwan University. "It became clear that these celecoxib analogues had a unique anti-bacterial activity, and they appeared to be most potent against Staph aureus and other MRSA strains."

The researchers narrowed the library down to a single agent (dubbed "compound 46") and moved to testing in MRSA-infected mice. Published in the August issue of Bioorganic and Medicinal Chemistry, the authors report that an intraperitoneal administration of compound 46 resulted in increased survival in MRSA-infected mice versus untreated mice.

"It was particularly gratifying to see that these compounds, originally designed as anticancer agents, work as a novel class of anti-bacterial agents based on the same principle in bacterial cells," said Chen.

The researchers are hopeful that this early work will ultimately provide insights on the development of a treatment for antibiotic resistant infectious diseases. The team is already working with scientists at the Ohio State Center for Microbial Interface Biology, led by Dr. Larry Schlesinger, to use this technology to develop novel agents against tuberculosis, another public health threat facing similar issues with drug resistance.

MRSA DNA tells scientists where it's been – and where it might go next

Investigators in the Division of Infectious Diseases at The Ohio State College of Medicine and Wexner Medical Center have created a statewide "roadmap" of that is helping them better predict how – and where – MRSA will spread.

The team, funded by the Centers for Disease Control and Prevention (CDC), used diverse methods from geographic analysis to molecular genotyping to track more than 1,000 MRSA cases from the Wexner Medical Center and community hospitals across Ohio. Experts say using a variety of tracking methods is essential to stopping infections before they start.

"With data from different sources, we've markedly improved our understanding of how MRSA is acquired and then spread among healthcare facilities. For example, we identified a very rare strain in the US, ST-239, which originated in Asia, spread to hospitals in Western Europe, and was introduced to Ohio sometime in the past two decades. It's that level of knowledge that will help us change the course of transmission," said Stevenson, whose research on ST-239 and its presence in healthcare facilities was published online ahead of print in the October issue of Emergent Infectious Diseases.

Using funding from the CCTS, investigators further applied diverse tracking methods to bloodstream isolates from hospitals in Franklin County, Ohio, as well as skin and soft tissue infections among patients receiving primary care in a variety of settings. The results not only demonstrated the value of rapid molecular typing in examining the distribution and transmission of individual MRSA strains, but showed that particular strains tended to cluster in specific places.

"These studies have demonstrated that specific molecular types of MRSA are linked to specific types of infections, or even specific settings. For instance, there are strains that tend to colonize catheters, strains that are more commonly found in nursing homes," said Shu-hua Wang, assistant professor of , who worked with Stevenson as part of a mentorship grant from the CCTS. "As we understand why certain MRSA strains behave as they do, more targeted interventions for prevention and treatment can be tested."

Stevenson is hopeful that technology will someday provide a quick and inexpensive on-site genomic analysis of MRSA. In anticipation of that day, the team is using the "roadmap" data to create a MRSA molecular library that provides a detailed background on individual strains, including its drug resistance, weaknesses, and most likely source of transmission.

"We're envisioning a future where every patient admitted into a hospital will get a rapid, strain-specific MRSA test and within minutes, a doctor will know exactly what protocol to follow to stop the patient from getting sick, and stop the bacteria from spreading," said Stevenson.

Explore further: MRSA superbug spreads from big city hospitals to regional health centers, study suggests

Related Stories

MRSA superbug spreads from big city hospitals to regional health centers, study suggests

May 14, 2012
Hospitals in large cities act as breeding grounds for the superbug MRSA prior to it spreading to smaller hospitals, a study suggests.

New type of MRSA in hospitalized patients probably of animal origin

June 2, 2011
A distinctly new type of methicillin resistant Staphylococcus aureus (MRSA) that is not detected by traditional genetic screening methods has been discovered in patients in Irish hospitals according to research to be published ...

Scientists find genes to beat MRSA defence system

June 20, 2011
Efforts to develop better and stronger treatments against diseases continue in Europe, with particular emphasis being placed on fighting human pathogens and strains resistant to existing treatments. Scientists in the United ...

Recommended for you

Pneumonia vaccine under development provides 'most comprehensive coverage' to date, alleviates antimicrobial concerns

October 20, 2017
In 2004, pneumonia killed more than 2 million children worldwide, according to the World Health Organization. By 2015, the number was less than 1 million.

Newly discovered viral marker could help predict flu severity in infected patients

October 20, 2017
Flu viruses contain defective genetic material that may activate the immune system in infected patients, and new research published in PLOS Pathogens suggests that lower levels of these molecules could increase flu severity.

H7N9 influenza is both lethal and transmissible in animal model for flu

October 19, 2017
In 2013, an influenza virus that had never before been detected began circulating among poultry in China. It caused several waves of human infection and in late 2016, the number of people to become sick from the H7N9 virus ...

Flu simulations suggest pandemics more likely in spring, early summer

October 19, 2017
New statistical simulations suggest that Northern Hemisphere flu pandemics are most likely to emerge in late spring or early summer at the tail end of the normal flu season, according to a new study published in PLOS Computational ...

New insights into herpes virus could inform vaccine development

October 18, 2017
A team of scientists has discovered new insights into the mechanisms of Epstein-Barr virus (EBV) infection, as well as two antibodies that block the virus' entry into cells. The findings, published in Proceedings of the National ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.