“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,
an
infectious disease expert at Ohio
State, and primary investigator of one of the studies
following the transmission of MRSA infections in communities. “While we’ve seen a decrease in the number of MRSA cases,
identifying new drug treatments and tracking methods will be critical to
stopping these infections before they can start.”
Cancer treatment
search leads scientists to MRSA killer, immune booster
In the August issue of Bioorganic and Medicinal Chemistry, researchers detail the results of a study that began 10 years
ago, when Ching-Shih Chen, professor of medicinal chemistry at Ohio State
College of Pharmacy, and a team of researchers were creating a library of
anti-cancer agents built around he 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 OSU-03012 acted within
breast cancer cells, Hao-Chieh Chiu, a then postdoctoral researcher in Chen’s
laboratory, realized that the derivatives were suppressing a mechanism that
bacteria use to take over their host cells. Chiu decided, with the support of
Dr. Chen, to focus his research on testing this compound library against a
variety of bacteria.
“When these 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 now
an assistant professor at the Department of Clinical Laboratory Sciences and Medical
Biotechnology at National
Taiwan University. “It became clear that these 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 have created a statewide
“roadmap” of MRSA infections 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 just published online in the October issue of Emergent
Infectious Diseases.
Stevenson’s team has also applied these 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 infectious disease. “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.
Both the drug development and community tracking
studies were funded by the Ohio State Center for Clinical and Translational
Science 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 the virulent bacteria spreads.
# # #
Contact: David Crawford, Wexner Medical
Center Public Affairs and
Media Relations, 614-293-3737, or Crawford.1@osu.edu